The experimental granuloma: a hypothesis to explain the persistence of the lesion

Mariano, M

doi:10.1590/S0036-46651995000200012

Abstracts

Granulomatous inflammation is the morphological substrate of a variety of important infectious diseases such as tuberculosis, leprosy, schistosomiasis and others. Nevertheless, although many aspects of this special type of inflammation are known, fundamental questions concerning granuloma formation, persistence, fate and significance for host-parasite relationships still remain to be elucidated. In this brief review, the basic and more relevant literature related to experimental investigations on granuloma physiopathology is presented. Based on recent investigations performed in our laboratory showing that MDF (Macrophage Deactivating Fator) secreted by epithelioid cells and characterized as the calcium-binding protein protein MRP-14 deactivates activated macrophages, a hypothesis to explain the persistence of granulomatous inflammation is put forward

Macrophage; Epithelioid cell; MDF; MRP-14; Granulona; Granulomatous inflammation

A inflamação glanulomatosa é o substrato morfológico de uma variedade de doenças infecciosas importantes tais como tuberculose, lepra, esquistossomose e outras. Embora muitos aspectos deste tipo especial de inflamação sejam conhecidos, questões fundamentais referentes à formação do granulona, persistência, destino e significado da relação hospedeiro-parasita permanecem para serem elucidados. Nesta revisão é apresentada a literatura básica e mais relevante relacionada à investigação experimental sobre a fisiopatologia do granuloma. Baseados em investigações recentes realizadas, em nosso laboratório mostrando que o fator de desativação do macrófago (MDF) secretado pelas células epitelióides e caracterizado pela proteína MRP-14, uma proteína ligante de cálcio, foi levantada hipótese para explicar a persistência da inflamação granulomatosa.

INVITED REVIEW

The experimental granuloma. A hypothesis to explain the persistence of the lesion

O granuloma experimental. Uma hipótese para explicar a persistência da lesão

M. Mariano

Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brasil

^{Correspondence to} Correspondence to: Prof. Mario Mariano Av. Prof. Lineu Prestes, 2415 Cidade Universitária - 05508-900 São Paulo, SP, Brasil Fone: (011) 818 7375 - Fax: (011) 813 0845 E-mail: mmariano@fox.cce.usp.br

SUMMARY

Granulomatous inflammation is the morphological substrate of a variety of important infectious diseases such as tuberculosis, leprosy, schistosomiasis and others. Nevertheless, although many aspects of this special type of inflammation are known, fundamental questions concerning granuloma formation, persistence, fate and significance for host-parasite relationships still remain to be elucidated. In this brief review, the basic and more relevant literature related to experimental investigations on granuloma physiopathology is presented. Based on recent investigations performed in our laboratory showing that MDF (Macrophage Deactivating Fator) secreted by epithelioid cells and characterized as the calcium-binding protein protein MRP-14 deactivates activated macrophages, a hypothesis to explain the persistence of granulomatous inflammation is put forward.

Keywords: Macrophage; Epithelioid cell; MDF; MRP-14; Granulona; Granulomatous inflammation.

RESUMO

A inflamação glanulomatosa é o substrato morfológico de uma variedade de doenças infecciosas importantes tais como tuberculose, lepra, esquistossomose e outras. Embora muitos aspectos deste tipo especial de inflamação sejam conhecidos, questões fundamentais referentes à formação do granulona, persistência, destino e significado da relação hospedeiro-parasita permanecem para serem elucidados. Nesta revisão é apresentada a literatura básica e mais relevante relacionada à investigação experimental sobre a fisiopatologia do granuloma. Baseados em investigações recentes realizadas, em nosso laboratório mostrando que o fator de desativação do macrófago (MDF) secretado pelas células epitelióides e caracterizado pela proteína MRP-14, uma proteína ligante de cálcio, foi levantada hipótese para explicar a persistência da inflamação granulomatosa.

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ACKNOWLEDGMENTS

The constructive criticisms of this review by Werner Haas, Cord Sunderkötter, Clemens Sorg and Sonia Jancar are gratefully acknowledged.

Recebido para publicação em 13/07/1994

Aceito para publicação em 08/09/1994

1. ADAMS, D.O. - The granulomatous inflammatory response. Amer. J. Path., 84: 164-191, 1976.
2. ADAMS, D.O. - The structure of mononuclear phagocytes differentiation "in vivo". 1. Sequencial fine and histologic studies of the effect of Bacillus Calmette-Guerin (BCG). Amer. J. Path., 76: 17-48, 1974.
3. ALLRED, C.; KOBAYASHI, K. & YOSHIDA, T. - Anergy-like immunosuppression in mice bearing pulmonary foreign-body granulomatous inflammation. Amer. J. Path. 121: 466-473, 1989.
4. ASCHOFF, L. - Tratado de anatomia patologica. Barcelona, Ed. Labor, 1950. p. 546-555.
5. AUGER, M.J. & ROSS, J.A. - The biology of macrophage. In: LEWIS, C. E. & O'D.McGEE, J., ed -. The natural immune system: the macrophage. Oxford, Oxford University Press, 1992. p. 1-57.
6. BENTLEY, A.G.; DOUGHTY, B.L. & PHILIPS, S.M. - Ultraestructral analysis of the cellular response to Schistosoma mansoni. III. The "in vitro" granuloma. Amer. J. trop. Med. Hyg., 3: 1168-1180, 1982.
7. BIKIERKUNST, A.; LEVY, I.S.; YARKONI, E, ADAM, A. & LEDERER, E. - Granuloma formation induction in mice by chemically defined mycobacterial fractions. J. Bact., 100: 95-102, 1969.
8. BIRMAN, E.G. & MARIANO, M. - The influence of inflammatory agents on giant cell formation. Braz. J. med. biol. Res., 18: 507-512, 1985.
9. BIRMAN, E.G. & MARIANO, M. - The modification of macrophage activity in experimental granulomas by cyclophosphamide. J. Path., 134: 133-146, 1981.
10. BONNEY, R.J. & DAVIES, P. - Possible autoregulatory functions of the secretory products of mononuclear phagocytes. In: ADAMS, D.O. & HANNA Jr., M.G. - Macrophage activation. Contemp. Top. Immunobiol., 13: 199-218, 1984.
11. BOROS, D.L. & WARREN, K.S. - The bentonite granuloma: characterization of a model system for infectious and foreign body granulomatous inflammation using soluble mycobacterial, histoplasma and Schistosoma antigens. Immunology, 24: 511-529, 1973.
12. BOROS, D.L. -. Granulomatous inflammation. Progr. Allergy, 24: 183-267, 1978.
13. BROWETT, P.J.; SIMPSPON, L.O. & BLENNERHASSETT, B. - Experimental granulomatous inflammation: the ultraestructure of the granuloma induced by injection of tubercle bacilli into Freund adjuvant-sensitized guinea-pigs. J. Path. 129: 191-201, 1979.
14. CALICH, V.L.G.; COPPI VAZ, C.A. & BURGER, E. - PMN chemotactic factor produced by glass-adherent cells in the acute inflammation caused by Paracoccidioides brasiliensis. Brit. J. exp. Path.. 66: 57-65, 1985.
15. CALICH, V.L.G.; KIPNIS, T.L.; MARIANO, M.; FAVA NETO, C. & DIAS DA SILVA, W. - The activation of the complement system by Paracoccidioides brasiliensis "in vitro": its opsonic effect and possible significance for an "in vivo" model of infection. Clin. Immunol. Immunopath., 12: 20-30, 1979.
16. CALMETTE, A. - L' infection bacillaire et la Tuberculose chez l'homme et chez les animaux. 4. ed. (Boquet, L.) Negre Paris, Masson, 1936, p.422-740.
17. CAMARERO, V.C.P.C.; COLEPICOLO, P.; RIBEIRO, J.M.C. & KARNOVSKY, M.L. - Leukocyte-deactivating factor from macrophages: partial purification and biochemical characterization. A novel cytokine. J. cell. Physiol., 157: 84-89, 1993.
18. CAMARERO, V.C.P.C.; JUNQUEIRA, V.; COLEPICOLO, P.; KARNOVSKY, M.L. & MARIANO, M. - Epithelioid macrophages secrete a deactivating factor for superoxide release. J. cell. Physiol., 145: 481-487, 1990.
19. CHAMBERS, T.J. - Failure of altered macrophage surface to lead to formation of polykaryons. J. Path., 122: 185-189, 1977.
20. CHAMBERS, T.J. - Multinucleate giant cells. J. Path.,126: 125-148, 1978.
21. CHEHL, S.; RUBY, J.; JOB, C.K. & HASTINGS, R.C. - The growth of Mycohacterium leprae in nude mice. Lepr. Rev., 54: 283-304, 1983.
22. CHENSUE, S.W. & BOROS, D.L. - Modulation of granulomatous hypersensitivity. I. Characterization of T-lymphocytes involved in the adoptive supression in Schistosoma mansoni-infected mice. J. Immunol., 123: 1409-1414, 1979.
23. CHENSUE, S.W.; BOROS, D.L. & DAVID, C.S. - Regulation of granulomatous inflammation in murine schistosomiasis. "In vitro" characterization of T lymphocyte subsets involved in the production and suppression of migration inhibitor factor. J. exp. Med., 151: 1398-1412, 1980.
24. CHENSUE, S.W.; WELLHAUSEN, S.R. & BOROS, D.L. - Modulation of granulomatous hypersensitivity. II. Participation of Ly1+ and Ly2+t lymphocytes in the suppression of granuloma formation and lymphokine production in Schistosoma mansoni infected mice. J. Immunol., 127: 363-367, 1981.
25. COURTADE, E.T.; TSUDA, T.; THOMAS, C.R. & DANNEMBERG Jr., A.M. - .Capillary density in developing and healing tuberculous lesions produced by BCG in rabbits: a quantitative study. Amer. J. Path., 78: 243-260, 1975.
26. DANNEMBERG Jr., A.M.; ANDO, M.; SHIMA, K. & TSUDA, T. - Macrophage turnover and activation in tuberculous granulomata. In: FURTH, R. Van, ed. - Mononuclear phagocytes in immunity infection and pathology. Oxford, Blackwell, 1975. p. 959-967
27. DE BRITO, T. & FRANCO, M.F. - Granulomatous inflammation. Rev. Inst. Med. trop. S. Paulo, 36: 185-192, 1994.
28. DE BRITO, T.; HOSHINO-SHIMIZU, S. & SILVA, L.C. - Immunopathology of experimental schistosomiasis (S. mansoni) egg granulomas in mice: possible defense mechanisms mediated by local immune complexes. J. Path., 140: 1-28, 1983.
29. DE BRITO, T.; HOSHINO-SHIMIZU, S.; SILVA, L.C. et al. - Chronic human schistosomiasis mansoni: schistosomal antigens, immunoglobulins and complement C3 detection in the liver. Liver, 5: 64-70, 1985.
30. DEFAVERI, J.; REZICALLAH, M.T. & FRANCO, M.F. -. Experimental paracoccidiodomycosis in mice: morphology and correlation of lesions with humoral and immune response. Mycopathologia (Den Haag), 77: 3-11, 1982.
31. DELABIE, J.; DE WOLF-PEETERS, C.; VAN DEN OORD, J.J. & DESMET, V.J. - Differential expression of the calcium-binding proteins MRP-8 and MRP-14 in granulomatous conditions: an immunohistochemical study. Clin. exp. Immunol., 81: 123-126, 1990.
32. DELOVITCH, T.L.; PHILLIPS, L.M.; NAQUET, P. et al. - Antigen internalization, processing, and recycling by antigen-presenting cells. Progr. Immunol., 6: 238-253, 1986.
33. DOUGHTY, B.L. & PHILLIPS, S.M. - Delayed hypersensitivity granuloma formation around Schistosoma mansoni eggs "in vitro". I Definition of the model. J. Immunol., 128: 30-36, 1982.
34. DOUGHTY, B.L. & PHILLIPS, S.M. - Delayed hypersensitivity granuloma formation and modulation around Schistosoma mansoni eggs "in vitro". II. Regulatory T cell subsets. J. Immunol., 128: 37-42, 1982.
35. DUNCAN, E.S. & STEWARD-TULL. -. Mycohacterium leprae. The bacteriologist's enigma. In: RATLEDGE, C., ed. - The biology of the mycobacteria. Stanford, Academic Press, 1982. p. 273-298.
36. DUNGWORTH, D.L. - The respiratory system. In: JUBB, K.V.F.; KENNEDY, P.C. & PALMER, N., ed. - Pathology of domestic animals. London, Academic Press, 1985. v.2, p 413-556.
37. DUNSFORD, H.A.; LUCIA, H.L.; DOUGHTY, B.L. & LICHTENBERG, F. VON - Artificial granulomas from bentonite and latex carrier particles. Amer. J. trop. Med. Hyg., 23: 203-217, 1974.
38. EPSTEIN W.L.; SKAHEN, J.R. & KLEBANOFF., S. J. -. Granulomatous hypersensitivity to zirconium: localization of allergen in tissue and its role in formation of epithelioid cells. J. invest. Derm., 38: 223-232, 1962.
39. EPSTEIN, W.L. - Granulomatous hypersensitivity. Progr. Allergy, 11: 36-88, 1967.
40. EPSTEIN, W.L.; OKAMOTO, M.; SUYA, H. & FUKUYAMA, K. - T-cell independent transfer of organized granuloma formation. Immunol. Lett., 14: 59-63, 1987.
41. GALINDO, B. & MYRVIK, Q.N. - Migratory response of granuiomatous alveolar cells from sensitized rabbits. J. Immunol., 105: 227-237, 1970.
42. GARCIA-LEME, J. - Role of lymphocytes in non-immune experimental inflammation. Agents and Actions, 11: 597-602, 1981.
43. GERSHON, R.K.; CARTER, R.L. & KONDO, K. - On concomitant immunity in tumor bearing hamsters. Nature (Lond.), 213: 674-676, 1967.
44. GILLMAN, T. & WRIGHT, L.J. - Probable "in vivo" origin of multinucleated giant cells from circulating mononuclears. Nature (Lond.), 209: 263-265, 1966.
45. GORDON, S.; LAWSON, L.; RABINOWITZ, P.R. et al. - Antigen markers of macrophage differentiation in murine tissue. Curr. Top. Microbiol. Immunol., 181: 1-37, 1992.
46. GRECCHI, R.; SALIBA, A.M. & MARIANO, M. - Morphological changes, surface receptors and phagocytic potencial of fowl mononuclear phagocytes and thrombocytes "in vivo" and "in vitro". J. Path., 130: 23-31, 1980.
47. HAMILTON, T.A.; RIGSBEE, J.A.; SCOTT, W.A. & ADAMS, D.O. - Gamma interferon enhances the secretion of arachidonic acid metabolites from murine peritoneal macrophages stimulated with phorbol derivatives. J. Immunol., 134: 2631-2637, 1985.
48. HANSEN, G.H.A. - On the ethiology of leprosy. Chirurg. Rev., 55: 459-489, 1875.
49. HESSIAN, P.A.; EDGEWORTH, J. & HOGG, N. - MRP-8 and MRP-14, two abundant Ca2'-binding proteins of neutrophils and mono-cytes. J. Leuk. Biol., 53: 197-204, 1993.
50. HIRASHIMA, M.; TASHINO, K.; SAKATA, K. & HIRSHIMA, M. - Isolation of an eosinophil chemotactic lymphokine as a natural mediator for eosinophil Chemotaxis from concanavalin A-induced skin reaction sites in guinea pigs. Clin. exp. Immunol., 57: 211-217, 1984.
51. HUBSCHER, T. & ELSEN, A.M. - An eosinophil derived inhibitor (EDI) of histamine release. J. Allergy clin. Immunol., 51: 671-676, 1975.
52. JAMES, S.L. & COLLEY, D.G. - Eosinophil-mediated destruction of Schistosoma mansoni eggs in vitro. II. Role of cytophilic antibody. Cell Immunol., 38: 35-47, 1978.
53. JONG, E.C.; HENDERSON, W.J. & KLEBANOFF, S.J. - Bactericidal activity of eosinophil peroxidase. J. Immunol., 124: 1378-1382, 1980.
54. KASAHARA, K.; KOBAYASHI, K.; SHIKAMA, Y. et al. - Direct evidence for granuloma-inducing activity of interleukin-1. Induction of experimental pulmonary granuloma formation in mice by interleukin-1 coupled beads. Amer. J. Path., 130: 629-638, 1988.
55. KINDLER, V.; SAPPINO, A.P.; GRAU, G.E.; PIGUET, P.F. & VASSALLI, P. - The inducing role of tumor necrosis factor in the development of bacterial granulomas during BCG infection. Cell, 56: 731-740, 1989.
56. KLIGMAN, D. & HILT, D.C. - The S-100 protein famili. Trends Biochem. Sci., 13: 437-443, 1988.
57. LAMMIE, P.J.; LINETTE, G.P. & PHILLIPS, M. - Characterization of Schistosoma mansoni antigen-reactive T cell clones that form granulomas in vitro. J. Immunol., 134: 4170-4175, 1985.
58. LASSER, A. - The mononuclear phagocytic system: a review. Hum. Path., 14: 108-126, 1983.
59. MARIANO, M. & FERREIRA, S.A. - BCG infection induces responsiveness to dead Mycohacterium leprae in hamsters. A Mitsuda like reaction. Braz. J. med. biol. Res., 22: 81, 1989.
60. MARIANO, M. & MALUCELLI, B.E. - Defective phagocytic ability of epithelioid cells reversed by levamisole. J. Path., 130: 33-36, 1980.
61. MARIANO, M. & SPECTOR. W.G. - The formation and properties of macrophage polykarions (Inflammatory giant cells). J. Path., 113: 1-19, 1974.
62. MARIANO, M. - Does macrophage deactivating factor play a role in the maintenance and fate of infectious granulomata? Mem. Inst. Oswaldo Cruz, 86; 485, 1991.
63. MARIANO, M.; AGUIAR, T.; CARNEIRO, C.R.W. et al. - Antibodies directed to antigens secreted by murine epithelioid macrophages modulate BCG-induced granulomata. Mediators Inflammation, 2: 229-233, 1993.
64. MARIANO, M.; NIKITIN, T. & MALUCELLI, B.E. -. Immunological and non-immunological phagocytosis by inflammatory macrophages, epithelioid cells and macrophage polykarions from foreign body granulomata. J. Path., 120: 151-159, 1976.
65. MARIANO, M.; NIKITIN, T. & MALUCELLI, B.E. - Phagocytic potencial of macrophages from within delayed hypersensitivity-mediated granulomata. J. Path., 3: 27-33, 1977.
66. MATHEW, R.C.; KATAYAMA, I.; GUPTA, S.K.; CURTIS, J. & TURK, J.L. - Analysis of cells of mononuclear phagocyte series in experimental mycobacterial granulomas by monoclonal antibodies. Infect. Immun., 39: 344-352, 1993.
67. McCLUSKEY, R.T.; BENACERRAF, B. & McCLUSKEY, J.W. - Studies on the specificity of the cellular infiltrate in delayed-type hypersensitivity reactions. J. Immunol., 90: 466-472, 1963.
68. McELRATH, M.J.; MURRAY, H.W. & COHN, Z.A. - The dynamics of granuloma formation in experimental visceral leishmaniasis. J. exp. Med., 164: 1927-1937, 1988.
69. McINNES, A. & RENNICK, D.M. - Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells. J. exp. Med., 167: 598, 1988.
70. MELRO, M.C.F. & MARIANO, M. -. Extra-tissular S. mansoni egg granuloma in the peritoneal cavity of mice. Mem. Inst. Oswaldo Cruz, 82 (suppl. 4): 245, 1987.
71. MONIS, B.; WEINEBERG, T. & SPECTOR, G.J. - The carrageenan granuloma in the rat. A model for the study of the structure and function of macrophages. Brit. J. exp. Path., 49: 302-310, 1968.
72. MONTENEGRO, M.R. & FRANCO, M. - Pathology. In: FRANCO, M.; LACAZ, C. da S.; RESTREPO-MORENO, A & DEL NEGRO, G., ed - Paracocciilioidomicosis. Boca Raton. CCR Press, 1993. p. 131-147.
73. MOURA, A.C.N. & MARIANO, M. - Dead Mycobaterium leprae inhibits phagocytosis by inflammatory macrophages in vivo. Participation of the bacterial cell lipids in the phenomenon. Mem. Inst. Oswaldo Cruz, 85: 381-382, 1990.
74. NATHAN, C.F. - Secretory products of macrophages. J. clin. Ąnvest.,79: 319-326, 1987.
75. NORTH, R.J. & IZZO, A.A. - Granuloma formation in severe combined immunodeficient (SCID) mice in response to progressive BCG infection. Tendency not to form granulomas in the lung is associated with faster bacterial growth in this organ. Amer. J. Path., 142: 1959-1966, 1993.
76. ODINK, K.; CERLETTK, N.; BRÜGGEN, J. et al. - Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. Nature, (Lond.) 330: 80-82, 1987.
77. OTTOWICZ, J.; ZAJUSZ, K.; NOWAK, B. & PARADOWSKI, Z. - The influence of immunologic factors on the development of experimental silicosis in guinea pigs. Arch. Immunol. Ther. exp., 15: 191-203, 1967.
78. PAGE, R.C.; DAVIES, P. & ALLISON, A.C. - Pathogenesis of the chronic inflammatory lesions induced by Group A streptococcal cell wall. Lab. Invest., 30: 568-581, 1974.
79. PAPADIMITRIOU, J.M. & SPECTOR, W.G. - The origin, properties and fate of epithelioid cells. J. Path., 105: 187-203, 1971.
80. PAPADIMITRIOU, J.M.; ROBERTSON, T.A. & WALTERS, N.I. - An analysis of the phagocytic potencial of multinucleated foreign body giant cells. Amer. J. Path., 78: 343-358, 1975.
81. PERAÇOLI, M.T.S.; MOTA, N.G.S. & MONTENEGRO, M.R. - Experimental paracoccidioidomycosis in Syrian hamster: morphology and correlation of lesions with humoral and cell-mediated immunity. Mycopathologia (Den Haag), 76: 7-12, 1982.
82. PHILLIPS, S.M. & COLLEY, G.D. - Immunologic aspects of host response to schistosomiasis: resistance, immunopathology, and eosinophil involvement. Progr. Allergy, 24: 49-57, 1978.
83. PRPIC, V.; WEIEL, J.E.; SOMERS, S.D. et al. - Effects of bacterial lipopolysaccharide on the hydrolysis of phosphatidylinositol 4,5-bis phosphate in murine peritoneal macrophages. J. Immunol., 139: 526-531, 1987.
84. RALPH, P.; HO, M.; LITCOFSKY, P.B. & SPRINGER, T.A. - Expression and induction in vitro of macrophages differentiation antigens on murine cell lines. J. Immunol., 130: 108-114, 1983.
85. RATNER, S. & VISON, S.B. - Phagocytosis and encapsulation. Cellular immune response in Arthropoda. Amer. Zool., 23: 185-194, 1983.
86. ROTH, J.; SUNDERKÖTTER, C.; GOEBELER, J. & SORG, C. Expression of the calcium-binding proteins MRP-8 and MRP-14 by early infiltrating cells in experimental contact dermatitis. Int. Arch. Allergy, 98: 140-145, 1992.
87. RYAN, G.B. & SPECTOR, W.G. - Macrophage turnover in inflammed connective tissue. Proc. roy. Soc. B., 175: 269-292, 1970.
88. RYAN, G.B. & SPECTOR, W.G. - Natural selection of long-lived macrophages in experimental granuloma. J. Path., 99: 139-136, 1969.
89. SHEPARD, C.C. - The experimental disease that follows the injection of human leprosy bacilli into mouse foot-pad of mice. J. exp. Med., 112: 445-454, 1960.
90. SHIKAMA, Y.; KOBAYASHI, K.; KASAHARA, K. et al. - Granuloma formation by artificial microparticles in vitro. Macrophages and monokines play a critical role in granuloma formation. Amer. J. Path., 134: 1189-1199, 1989.
91. SINHORINI, I.L.; MERUSSE, J.L.B. & MARIANO, M. - Role of lymphatic drainage on the development of Calmette-Guérin Bacillus-induced granulomas in the hamster. Int. Arch. Allergy., 103: 166-174, 1994.
92. SMITH, S.L. & COLLEY, D.G. - The ultraestructural development of Schistosoma egg granuloma in mice. Parasitology, 75: 119-123, 1977.
93. SOMERS, S.D.; WEIEL, J.E.; HAMILTON, T.A. & ADAMS, D.O. - Phorbol esters and calcium ionophore can prime murine peritoneal macrophages for tumor cell destruction. J. Immunol., 136: 4199-4204, 1986.
94. SPECTOR, W.G. & LYKKE, A.W.J. - The cellular evolution of inflammatory granulomata. J. Path. Bact., 92: 163-167, 1966.
95. SPECTOR, W.G. & RYAN, G.B. - New evidence for the existence of long lived macrophages. Nature (Lond.), 221: 860, 1969.
96. SPECTOR, W.G. & WILLOUGHBY, D.A. - The origin of mononuclear cells in chronic inflammation and tuberculin reactions in the rat. J. Path. Bact., 96: 389-399, 1968.
97. SPECTOR, W.G.; HEESOM, N. & STEVENS, J.E. - Factors influencing chronicity in inflammation of rat skin. J. Path. Bact., 96: 203-213, 1968.
98. SPECTOR, W.G.; REICHOLD, N. & RYAN, G.B. - Degradation of granuloma-inducing microorganisms by macrophages. J. Path., 101: 339-354, 1970.
99. SPECTOR, W.G. & MARIANO, M. - Macrophage behaviour in experimental granulomas. In: FURTH, R. van, ed. - Mononuclear phagocytes in immunity infection and pathology. Oxford, Blackwell, 1975. p. 959-968.
100. STADECKER, M.J. & WRIGHT, J.A. - Distribution and kinetics of mononuclear phagocytes in granulomas elicited by eggs of Schistosoma mansoni. Amer. J. Path., 116: 245-252, 1984.
101. STADECKER, M.J.; WYLER, D.J. & WRIGHT, J.A. - Ia antigen expression and antigen presenting function by macrophages isolated from hypersensitivity granulomas. J. Immunol., 128: 2739-2744, 1981.
102. STOSSEL, T.P. - Phagocytosis. New. Engl. J. Med., 290: 717-723, 1974.
103. STOSSEL, T.P. - Phagocytosis: recognition and ingestion. Semin. Hemat., 12: 83-116, 1975.
104. SUNDERKÖTTER, C.; BEIL, W.; ROTH, J. & SORG, C. - Cellular events associated with inflammatory angiogenesis in the mouse. Amer. J. Path., 138: 1-5, 1991.
105. SUTTON, J.S. & WEISS, L. - Transformation of monocytes in tissue culture into macrophages, epithelioid cells and multinucleated giant cells. An electron microscope study. J. Cell Biol., 28: 303-332, 1966.
106. TAKEMURA, A.I. & WERB, Z. - Secretory products of macrophages and their physiological function. Amer. J. Physiol., 246: C1-C9, 1984.
107. THOMAS, M.A. & MACSWEEN, R.N.M. - Heterogeneity of rat alveolar macrophage populations: characterization of their surface antigens by antisera. Brit. J. exp. Path., 62: 65-73, 1981.
108. TSUDA, T.; DANNEMBERG, A.M.; ANDO, M.; ABBEY, H. & CORRIN, A.R. - Mononuclear cell turnover in chronic inflammation. Amer. J. Path., 83: 255-268, 1976.
109. VACHER, J. - Immunological responses of guinea pigs to beryllium salts. J. med. Microbiol., 5: 91-108, 1972.
110. VAN DEN OORD, J.J.; WOLF-PEETERS, C.; FACCHETTI, F. & DESMET, V.J. - Cellular composition of hypersensitivity-type granulomas: immunohistochemical analysis of tuberculous and sarcoidal lymphadenitis. Hum. Path., 15: 559-565, 1984.
111. VAN DER RHEE, H.J.; VAN DER BURGH WINTER, C.P.M. & DAEMS, W.T. - The differentiation of monocytes into macrophages, epithelioid cells and multinucleated giant cells in subcutaneous granulomas. Cell Tiss. Res., 197: 355-378, 1979.
112. VOLKMAN, A. & GOWANS, J.L. - The production of macrophages in the rat. Brit. J. exp. Path., 46: 50-61, 1965.
113. WARREN, K.S. - Functional classification of granulomatous inflammation. Ann. N. Y. Acad. Sci., 278: 7-18, 1976.
114. WERB, Z. - How the macrophages regulate its extracelullar environment. Amer. J. Anat., 116: 237-256, 1983.
115. ZWALDO, G.; BRUGGEN, J.; GERHARDS, G.; SCHELEGGEL, R. & SORG, C. - Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. Clin. exp. Immunol., 72: 510-515, 1988.

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Prof. Mario Mariano

Av. Prof. Lineu Prestes, 2415

Cidade Universitária - 05508-900 São Paulo, SP, Brasil

Fone: (011) 818 7375 - Fax: (011) 813 0845

E-mail:

mmariano@fox.cce.usp.br

Publication Dates

Publication in this collection
22 Feb 2007
Date of issue
Apr 1995

History

Received
13 July 1994
Accepted
08 Sept 1994

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ADAMS, D.O. - The granulomatous inflammatory response. Amer. J. Path., 84: 164-191, 1976.

[2] 2. ADAMS, D.O. - The structure of mononuclear phagocytes differentiation "in vivo". 1. Sequencial fine and histologic studies of the effect of Bacillus Calmette-Guerin (BCG). Amer. J. Path., 76: 17-48, 1974.

[3] 3. ALLRED, C.; KOBAYASHI, K. & YOSHIDA, T. - Anergy-like immunosuppression in mice bearing pulmonary foreign-body granulomatous inflammation. Amer. J. Path. 121: 466-473, 1989.

[4] 4. ASCHOFF, L. - Tratado de anatomia patologica. Barcelona, Ed. Labor, 1950. p. 546-555.

[5] 5. AUGER, M.J. & ROSS, J.A. - The biology of macrophage. In: LEWIS, C. E. & O'D.McGEE, J., ed -. The natural immune system: the macrophage. Oxford, Oxford University Press, 1992. p. 1-57.

[6] 6. BENTLEY, A.G.; DOUGHTY, B.L. & PHILIPS, S.M. - Ultraestructral analysis of the cellular response to Schistosoma mansoni. III. The "in vitro" granuloma. Amer. J. trop. Med. Hyg., 3: 1168-1180, 1982.

[7] 7. BIKIERKUNST, A.; LEVY, I.S.; YARKONI, E, ADAM, A. & LEDERER, E. - Granuloma formation induction in mice by chemically defined mycobacterial fractions. J. Bact., 100: 95-102, 1969.

[8] 8. BIRMAN, E.G. & MARIANO, M. - The influence of inflammatory agents on giant cell formation. Braz. J. med. biol. Res., 18: 507-512, 1985.

[9] 9. BIRMAN, E.G. & MARIANO, M. - The modification of macrophage activity in experimental granulomas by cyclophosphamide. J. Path., 134: 133-146, 1981.

[10] 10. BONNEY, R.J. & DAVIES, P. - Possible autoregulatory functions of the secretory products of mononuclear phagocytes. In: ADAMS, D.O. & HANNA Jr., M.G. - Macrophage activation. Contemp. Top. Immunobiol., 13: 199-218, 1984.

[11] 11. BOROS, D.L. & WARREN, K.S. - The bentonite granuloma: characterization of a model system for infectious and foreign body granulomatous inflammation using soluble mycobacterial, histoplasma and Schistosoma antigens. Immunology, 24: 511-529, 1973.

[12] 12. BOROS, D.L. -. Granulomatous inflammation. Progr. Allergy, 24: 183-267, 1978.

[13] 13. BROWETT, P.J.; SIMPSPON, L.O. & BLENNERHASSETT, B. - Experimental granulomatous inflammation: the ultraestructure of the granuloma induced by injection of tubercle bacilli into Freund adjuvant-sensitized guinea-pigs. J. Path. 129: 191-201, 1979.

[14] 14. CALICH, V.L.G.; COPPI VAZ, C.A. & BURGER, E. - PMN chemotactic factor produced by glass-adherent cells in the acute inflammation caused by Paracoccidioides brasiliensis. Brit. J. exp. Path.. 66: 57-65, 1985.

[15] 15. CALICH, V.L.G.; KIPNIS, T.L.; MARIANO, M.; FAVA NETO, C. & DIAS DA SILVA, W. - The activation of the complement system by Paracoccidioides brasiliensis "in vitro": its opsonic effect and possible significance for an "in vivo" model of infection. Clin. Immunol. Immunopath., 12: 20-30, 1979.

[16] 16. CALMETTE, A. - L' infection bacillaire et la Tuberculose chez l'homme et chez les animaux. 4. ed. (Boquet, L.) Negre Paris, Masson, 1936, p.422-740.

[17] 17. CAMARERO, V.C.P.C.; COLEPICOLO, P.; RIBEIRO, J.M.C. & KARNOVSKY, M.L. - Leukocyte-deactivating factor from macrophages: partial purification and biochemical characterization. A novel cytokine. J. cell. Physiol., 157: 84-89, 1993.

[18] 18. CAMARERO, V.C.P.C.; JUNQUEIRA, V.; COLEPICOLO, P.; KARNOVSKY, M.L. & MARIANO, M. - Epithelioid macrophages secrete a deactivating factor for superoxide release. J. cell. Physiol., 145: 481-487, 1990.

[19] 19. CHAMBERS, T.J. - Failure of altered macrophage surface to lead to formation of polykaryons. J. Path., 122: 185-189, 1977.

[20] 20. CHAMBERS, T.J. - Multinucleate giant cells. J. Path.,126: 125-148, 1978.

[21] 21. CHEHL, S.; RUBY, J.; JOB, C.K. & HASTINGS, R.C. - The growth of Mycohacterium leprae in nude mice. Lepr. Rev., 54: 283-304, 1983.

[22] 22. CHENSUE, S.W. & BOROS, D.L. - Modulation of granulomatous hypersensitivity. I. Characterization of T-lymphocytes involved in the adoptive supression in Schistosoma mansoni-infected mice. J. Immunol., 123: 1409-1414, 1979.

[23] 23. CHENSUE, S.W.; BOROS, D.L. & DAVID, C.S. - Regulation of granulomatous inflammation in murine schistosomiasis. "In vitro" characterization of T lymphocyte subsets involved in the production and suppression of migration inhibitor factor. J. exp. Med., 151: 1398-1412, 1980.

[24] 24. CHENSUE, S.W.; WELLHAUSEN, S.R. & BOROS, D.L. - Modulation of granulomatous hypersensitivity. II. Participation of Ly1+ and Ly2+t lymphocytes in the suppression of granuloma formation and lymphokine production in Schistosoma mansoni infected mice. J. Immunol., 127: 363-367, 1981.

[25] 25. COURTADE, E.T.; TSUDA, T.; THOMAS, C.R. & DANNEMBERG Jr., A.M. - .Capillary density in developing and healing tuberculous lesions produced by BCG in rabbits: a quantitative study. Amer. J. Path., 78: 243-260, 1975.

[26] 26. DANNEMBERG Jr., A.M.; ANDO, M.; SHIMA, K. & TSUDA, T. - Macrophage turnover and activation in tuberculous granulomata. In: FURTH, R. Van, ed. - Mononuclear phagocytes in immunity infection and pathology. Oxford, Blackwell, 1975. p. 959-967

[27] 27. DE BRITO, T. & FRANCO, M.F. - Granulomatous inflammation. Rev. Inst. Med. trop. S. Paulo, 36: 185-192, 1994.

[28] 28. DE BRITO, T.; HOSHINO-SHIMIZU, S. & SILVA, L.C. - Immunopathology of experimental schistosomiasis (S. mansoni) egg granulomas in mice: possible defense mechanisms mediated by local immune complexes. J. Path., 140: 1-28, 1983.

[29] 29. DE BRITO, T.; HOSHINO-SHIMIZU, S.; SILVA, L.C. et al. - Chronic human schistosomiasis mansoni: schistosomal antigens, immunoglobulins and complement C3 detection in the liver. Liver, 5: 64-70, 1985.

[30] 30. DEFAVERI, J.; REZICALLAH, M.T. & FRANCO, M.F. -. Experimental paracoccidiodomycosis in mice: morphology and correlation of lesions with humoral and immune response. Mycopathologia (Den Haag), 77: 3-11, 1982.

[31] 31. DELABIE, J.; DE WOLF-PEETERS, C.; VAN DEN OORD, J.J. & DESMET, V.J. - Differential expression of the calcium-binding proteins MRP-8 and MRP-14 in granulomatous conditions: an immunohistochemical study. Clin. exp. Immunol., 81: 123-126, 1990.

[32] 32. DELOVITCH, T.L.; PHILLIPS, L.M.; NAQUET, P. et al. - Antigen internalization, processing, and recycling by antigen-presenting cells. Progr. Immunol., 6: 238-253, 1986.

[33] 33. DOUGHTY, B.L. & PHILLIPS, S.M. - Delayed hypersensitivity granuloma formation around Schistosoma mansoni eggs "in vitro". I Definition of the model. J. Immunol., 128: 30-36, 1982.

[34] 34. DOUGHTY, B.L. & PHILLIPS, S.M. - Delayed hypersensitivity granuloma formation and modulation around Schistosoma mansoni eggs "in vitro". II. Regulatory T cell subsets. J. Immunol., 128: 37-42, 1982.

[35] 35. DUNCAN, E.S. & STEWARD-TULL. -. Mycohacterium leprae. The bacteriologist's enigma. In: RATLEDGE, C., ed. - The biology of the mycobacteria. Stanford, Academic Press, 1982. p. 273-298.

[36] 36. DUNGWORTH, D.L. - The respiratory system. In: JUBB, K.V.F.; KENNEDY, P.C. & PALMER, N., ed. - Pathology of domestic animals. London, Academic Press, 1985. v.2, p 413-556.

[37] 37. DUNSFORD, H.A.; LUCIA, H.L.; DOUGHTY, B.L. & LICHTENBERG, F. VON - Artificial granulomas from bentonite and latex carrier particles. Amer. J. trop. Med. Hyg., 23: 203-217, 1974.

[38] 38. EPSTEIN W.L.; SKAHEN, J.R. & KLEBANOFF., S. J. -. Granulomatous hypersensitivity to zirconium: localization of allergen in tissue and its role in formation of epithelioid cells. J. invest. Derm., 38: 223-232, 1962.

[39] 39. EPSTEIN, W.L. - Granulomatous hypersensitivity. Progr. Allergy, 11: 36-88, 1967.

[40] 40. EPSTEIN, W.L.; OKAMOTO, M.; SUYA, H. & FUKUYAMA, K. - T-cell independent transfer of organized granuloma formation. Immunol. Lett., 14: 59-63, 1987.

[41] 41. GALINDO, B. & MYRVIK, Q.N. - Migratory response of granuiomatous alveolar cells from sensitized rabbits. J. Immunol., 105: 227-237, 1970.

[42] 42. GARCIA-LEME, J. - Role of lymphocytes in non-immune experimental inflammation. Agents and Actions, 11: 597-602, 1981.

[43] 43. GERSHON, R.K.; CARTER, R.L. & KONDO, K. - On concomitant immunity in tumor bearing hamsters. Nature (Lond.), 213: 674-676, 1967.

[44] 44. GILLMAN, T. & WRIGHT, L.J. - Probable "in vivo" origin of multinucleated giant cells from circulating mononuclears. Nature (Lond.), 209: 263-265, 1966.

[45] 45. GORDON, S.; LAWSON, L.; RABINOWITZ, P.R. et al. - Antigen markers of macrophage differentiation in murine tissue. Curr. Top. Microbiol. Immunol., 181: 1-37, 1992.

[46] 46. GRECCHI, R.; SALIBA, A.M. & MARIANO, M. - Morphological changes, surface receptors and phagocytic potencial of fowl mononuclear phagocytes and thrombocytes "in vivo" and "in vitro". J. Path., 130: 23-31, 1980.

[47] 47. HAMILTON, T.A.; RIGSBEE, J.A.; SCOTT, W.A. & ADAMS, D.O. - Gamma interferon enhances the secretion of arachidonic acid metabolites from murine peritoneal macrophages stimulated with phorbol derivatives. J. Immunol., 134: 2631-2637, 1985.

[48] 48. HANSEN, G.H.A. - On the ethiology of leprosy. Chirurg. Rev., 55: 459-489, 1875.

[49] 49. HESSIAN, P.A.; EDGEWORTH, J. & HOGG, N. - MRP-8 and MRP-14, two abundant Ca2'-binding proteins of neutrophils and mono-cytes. J. Leuk. Biol., 53: 197-204, 1993.

[50] 50. HIRASHIMA, M.; TASHINO, K.; SAKATA, K. & HIRSHIMA, M. - Isolation of an eosinophil chemotactic lymphokine as a natural mediator for eosinophil Chemotaxis from concanavalin A-induced skin reaction sites in guinea pigs. Clin. exp. Immunol., 57: 211-217, 1984.

[51] 51. HUBSCHER, T. & ELSEN, A.M. - An eosinophil derived inhibitor (EDI) of histamine release. J. Allergy clin. Immunol., 51: 671-676, 1975.

[52] 52. JAMES, S.L. & COLLEY, D.G. - Eosinophil-mediated destruction of Schistosoma mansoni eggs in vitro. II. Role of cytophilic antibody. Cell Immunol., 38: 35-47, 1978.

[53] 53. JONG, E.C.; HENDERSON, W.J. & KLEBANOFF, S.J. - Bactericidal activity of eosinophil peroxidase. J. Immunol., 124: 1378-1382, 1980.

[54] 54. KASAHARA, K.; KOBAYASHI, K.; SHIKAMA, Y. et al. - Direct evidence for granuloma-inducing activity of interleukin-1. Induction of experimental pulmonary granuloma formation in mice by interleukin-1 coupled beads. Amer. J. Path., 130: 629-638, 1988.

[55] 55. KINDLER, V.; SAPPINO, A.P.; GRAU, G.E.; PIGUET, P.F. & VASSALLI, P. - The inducing role of tumor necrosis factor in the development of bacterial granulomas during BCG infection. Cell, 56: 731-740, 1989.

[56] 56. KLIGMAN, D. & HILT, D.C. - The S-100 protein famili. Trends Biochem. Sci., 13: 437-443, 1988.

[57] 57. LAMMIE, P.J.; LINETTE, G.P. & PHILLIPS, M. - Characterization of Schistosoma mansoni antigen-reactive T cell clones that form granulomas in vitro. J. Immunol., 134: 4170-4175, 1985.

[58] 58. LASSER, A. - The mononuclear phagocytic system: a review. Hum. Path., 14: 108-126, 1983.

[59] 59. MARIANO, M. & FERREIRA, S.A. - BCG infection induces responsiveness to dead Mycohacterium leprae in hamsters. A Mitsuda like reaction. Braz. J. med. biol. Res., 22: 81, 1989.

[60] 60. MARIANO, M. & MALUCELLI, B.E. - Defective phagocytic ability of epithelioid cells reversed by levamisole. J. Path., 130: 33-36, 1980.

[61] 61. MARIANO, M. & SPECTOR. W.G. - The formation and properties of macrophage polykarions (Inflammatory giant cells). J. Path., 113: 1-19, 1974.

[62] 62. MARIANO, M. - Does macrophage deactivating factor play a role in the maintenance and fate of infectious granulomata? Mem. Inst. Oswaldo Cruz, 86; 485, 1991.

[63] 63. MARIANO, M.; AGUIAR, T.; CARNEIRO, C.R.W. et al. - Antibodies directed to antigens secreted by murine epithelioid macrophages modulate BCG-induced granulomata. Mediators Inflammation, 2: 229-233, 1993.

[64] 64. MARIANO, M.; NIKITIN, T. & MALUCELLI, B.E. -. Immunological and non-immunological phagocytosis by inflammatory macrophages, epithelioid cells and macrophage polykarions from foreign body granulomata. J. Path., 120: 151-159, 1976.

[65] 65. MARIANO, M.; NIKITIN, T. & MALUCELLI, B.E. - Phagocytic potencial of macrophages from within delayed hypersensitivity-mediated granulomata. J. Path., 3: 27-33, 1977.

[66] 66. MATHEW, R.C.; KATAYAMA, I.; GUPTA, S.K.; CURTIS, J. & TURK, J.L. - Analysis of cells of mononuclear phagocyte series in experimental mycobacterial granulomas by monoclonal antibodies. Infect. Immun., 39: 344-352, 1993.

[67] 67. McCLUSKEY, R.T.; BENACERRAF, B. & McCLUSKEY, J.W. - Studies on the specificity of the cellular infiltrate in delayed-type hypersensitivity reactions. J. Immunol., 90: 466-472, 1963.

[68] 68. McELRATH, M.J.; MURRAY, H.W. & COHN, Z.A. - The dynamics of granuloma formation in experimental visceral leishmaniasis. J. exp. Med., 164: 1927-1937, 1988.

[69] 69. McINNES, A. & RENNICK, D.M. - Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells. J. exp. Med., 167: 598, 1988.

[70] 70. MELRO, M.C.F. & MARIANO, M. -. Extra-tissular S. mansoni egg granuloma in the peritoneal cavity of mice. Mem. Inst. Oswaldo Cruz, 82 (suppl. 4): 245, 1987.

[71] 71. MONIS, B.; WEINEBERG, T. & SPECTOR, G.J. - The carrageenan granuloma in the rat. A model for the study of the structure and function of macrophages. Brit. J. exp. Path., 49: 302-310, 1968.

[72] 72. MONTENEGRO, M.R. & FRANCO, M. - Pathology. In: FRANCO, M.; LACAZ, C. da S.; RESTREPO-MORENO, A & DEL NEGRO, G., ed - Paracocciilioidomicosis. Boca Raton. CCR Press, 1993. p. 131-147.

[73] 73. MOURA, A.C.N. & MARIANO, M. - Dead Mycobaterium leprae inhibits phagocytosis by inflammatory macrophages in vivo. Participation of the bacterial cell lipids in the phenomenon. Mem. Inst. Oswaldo Cruz, 85: 381-382, 1990.

[74] 74. NATHAN, C.F. - Secretory products of macrophages. J. clin. Ąnvest.,79: 319-326, 1987.

[75] 75. NORTH, R.J. & IZZO, A.A. - Granuloma formation in severe combined immunodeficient (SCID) mice in response to progressive BCG infection. Tendency not to form granulomas in the lung is associated with faster bacterial growth in this organ. Amer. J. Path., 142: 1959-1966, 1993.

[76] 76. ODINK, K.; CERLETTK, N.; BRÜGGEN, J. et al. - Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. Nature, (Lond.) 330: 80-82, 1987.

[77] 77. OTTOWICZ, J.; ZAJUSZ, K.; NOWAK, B. & PARADOWSKI, Z. - The influence of immunologic factors on the development of experimental silicosis in guinea pigs. Arch. Immunol. Ther. exp., 15: 191-203, 1967.

[78] 78. PAGE, R.C.; DAVIES, P. & ALLISON, A.C. - Pathogenesis of the chronic inflammatory lesions induced by Group A streptococcal cell wall. Lab. Invest., 30: 568-581, 1974.

[79] 79. PAPADIMITRIOU, J.M. & SPECTOR, W.G. - The origin, properties and fate of epithelioid cells. J. Path., 105: 187-203, 1971.

[80] 80. PAPADIMITRIOU, J.M.; ROBERTSON, T.A. & WALTERS, N.I. - An analysis of the phagocytic potencial of multinucleated foreign body giant cells. Amer. J. Path., 78: 343-358, 1975.

[81] 81. PERAÇOLI, M.T.S.; MOTA, N.G.S. & MONTENEGRO, M.R. - Experimental paracoccidioidomycosis in Syrian hamster: morphology and correlation of lesions with humoral and cell-mediated immunity. Mycopathologia (Den Haag), 76: 7-12, 1982.

[82] 82. PHILLIPS, S.M. & COLLEY, G.D. - Immunologic aspects of host response to schistosomiasis: resistance, immunopathology, and eosinophil involvement. Progr. Allergy, 24: 49-57, 1978.

[83] 83. PRPIC, V.; WEIEL, J.E.; SOMERS, S.D. et al. - Effects of bacterial lipopolysaccharide on the hydrolysis of phosphatidylinositol 4,5-bis phosphate in murine peritoneal macrophages. J. Immunol., 139: 526-531, 1987.

[84] 84. RALPH, P.; HO, M.; LITCOFSKY, P.B. & SPRINGER, T.A. - Expression and induction in vitro of macrophages differentiation antigens on murine cell lines. J. Immunol., 130: 108-114, 1983.

[85] 85. RATNER, S. & VISON, S.B. - Phagocytosis and encapsulation. Cellular immune response in Arthropoda. Amer. Zool., 23: 185-194, 1983.

[86] 86. ROTH, J.; SUNDERKÖTTER, C.; GOEBELER, J. & SORG, C. Expression of the calcium-binding proteins MRP-8 and MRP-14 by early infiltrating cells in experimental contact dermatitis. Int. Arch. Allergy, 98: 140-145, 1992.

[87] 87. RYAN, G.B. & SPECTOR, W.G. - Macrophage turnover in inflammed connective tissue. Proc. roy. Soc. B., 175: 269-292, 1970.

[88] 88. RYAN, G.B. & SPECTOR, W.G. - Natural selection of long-lived macrophages in experimental granuloma. J. Path., 99: 139-136, 1969.

[89] 89. SHEPARD, C.C. - The experimental disease that follows the injection of human leprosy bacilli into mouse foot-pad of mice. J. exp. Med., 112: 445-454, 1960.

[90] 90. SHIKAMA, Y.; KOBAYASHI, K.; KASAHARA, K. et al. - Granuloma formation by artificial microparticles in vitro. Macrophages and monokines play a critical role in granuloma formation. Amer. J. Path., 134: 1189-1199, 1989.

[91] 91. SINHORINI, I.L.; MERUSSE, J.L.B. & MARIANO, M. - Role of lymphatic drainage on the development of Calmette-Guérin Bacillus-induced granulomas in the hamster. Int. Arch. Allergy., 103: 166-174, 1994.

[92] 92. SMITH, S.L. & COLLEY, D.G. - The ultraestructural development of Schistosoma egg granuloma in mice. Parasitology, 75: 119-123, 1977.

[93] 93. SOMERS, S.D.; WEIEL, J.E.; HAMILTON, T.A. & ADAMS, D.O. - Phorbol esters and calcium ionophore can prime murine peritoneal macrophages for tumor cell destruction. J. Immunol., 136: 4199-4204, 1986.

[94] 94. SPECTOR, W.G. & LYKKE, A.W.J. - The cellular evolution of inflammatory granulomata. J. Path. Bact., 92: 163-167, 1966.

[95] 95. SPECTOR, W.G. & RYAN, G.B. - New evidence for the existence of long lived macrophages. Nature (Lond.), 221: 860, 1969.

[96] 96. SPECTOR, W.G. & WILLOUGHBY, D.A. - The origin of mononuclear cells in chronic inflammation and tuberculin reactions in the rat. J. Path. Bact., 96: 389-399, 1968.

[97] 97. SPECTOR, W.G.; HEESOM, N. & STEVENS, J.E. - Factors influencing chronicity in inflammation of rat skin. J. Path. Bact., 96: 203-213, 1968.

[98] 98. SPECTOR, W.G.; REICHOLD, N. & RYAN, G.B. - Degradation of granuloma-inducing microorganisms by macrophages. J. Path., 101: 339-354, 1970.

[99] 99. SPECTOR, W.G. & MARIANO, M. - Macrophage behaviour in experimental granulomas. In: FURTH, R. van, ed. - Mononuclear phagocytes in immunity infection and pathology. Oxford, Blackwell, 1975. p. 959-968.

[100] 100. STADECKER, M.J. & WRIGHT, J.A. - Distribution and kinetics of mononuclear phagocytes in granulomas elicited by eggs of Schistosoma mansoni. Amer. J. Path., 116: 245-252, 1984.

[101] 101. STADECKER, M.J.; WYLER, D.J. & WRIGHT, J.A. - Ia antigen expression and antigen presenting function by macrophages isolated from hypersensitivity granulomas. J. Immunol., 128: 2739-2744, 1981.

[102] 102. STOSSEL, T.P. - Phagocytosis. New. Engl. J. Med., 290: 717-723, 1974.

[103] 103. STOSSEL, T.P. - Phagocytosis: recognition and ingestion. Semin. Hemat., 12: 83-116, 1975.

[104] 104. SUNDERKÖTTER, C.; BEIL, W.; ROTH, J. & SORG, C. - Cellular events associated with inflammatory angiogenesis in the mouse. Amer. J. Path., 138: 1-5, 1991.

[105] 105. SUTTON, J.S. & WEISS, L. - Transformation of monocytes in tissue culture into macrophages, epithelioid cells and multinucleated giant cells. An electron microscope study. J. Cell Biol., 28: 303-332, 1966.

[106] 106. TAKEMURA, A.I. & WERB, Z. - Secretory products of macrophages and their physiological function. Amer. J. Physiol., 246: C1-C9, 1984.

[107] 107. THOMAS, M.A. & MACSWEEN, R.N.M. - Heterogeneity of rat alveolar macrophage populations: characterization of their surface antigens by antisera. Brit. J. exp. Path., 62: 65-73, 1981.

[108] 108. TSUDA, T.; DANNEMBERG, A.M.; ANDO, M.; ABBEY, H. & CORRIN, A.R. - Mononuclear cell turnover in chronic inflammation. Amer. J. Path., 83: 255-268, 1976.

[109] 109. VACHER, J. - Immunological responses of guinea pigs to beryllium salts. J. med. Microbiol., 5: 91-108, 1972.

[110] 110. VAN DEN OORD, J.J.; WOLF-PEETERS, C.; FACCHETTI, F. & DESMET, V.J. - Cellular composition of hypersensitivity-type granulomas: immunohistochemical analysis of tuberculous and sarcoidal lymphadenitis. Hum. Path., 15: 559-565, 1984.

[111] 111. VAN DER RHEE, H.J.; VAN DER BURGH WINTER, C.P.M. & DAEMS, W.T. - The differentiation of monocytes into macrophages, epithelioid cells and multinucleated giant cells in subcutaneous granulomas. Cell Tiss. Res., 197: 355-378, 1979.

[112] 112. VOLKMAN, A. & GOWANS, J.L. - The production of macrophages in the rat. Brit. J. exp. Path., 46: 50-61, 1965.

[113] 113. WARREN, K.S. - Functional classification of granulomatous inflammation. Ann. N. Y. Acad. Sci., 278: 7-18, 1976.

[114] 114. WERB, Z. - How the macrophages regulate its extracelullar environment. Amer. J. Anat., 116: 237-256, 1983.

[115] 115. ZWALDO, G.; BRUGGEN, J.; GERHARDS, G.; SCHELEGGEL, R. & SORG, C. - Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. Clin. exp. Immunol., 72: 510-515, 1988.

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