Mini-Symposium - Abstracts
7 PATHOGENESIS OF MYONECROSIS INDUCED BY PLA2 MYOTOXINSFROM VARIOUS SOURCES
C.L. OWNBY
Department of Anatomy, Pathology and Pharmacology, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma. 74078, USA
Phospholipases A2 are enzymes that hydrolyze the 2- acyl group of phospholipids and release fatty acids and lysophospholipids. Although these phospholipases are very similar in their structure, they show remarkable diversity in their functional properties. Based on the primary sequence data, these enzymes can be categorized into at least three types. Type I contains enzymes from mammalian pancreas and venoms from snakes in the families Elapidae (cobras and kraits) and Hydrophidae (sea snakes) and from human spermatozoa. Type II includes enzymes in the venoms of snakes in the family Viperidae, subfamily Crotalinae (pit vipers) and Viperinae(true vipers) as well as some mammalian cell types, including platelets, gastric mucosae and vascular endothelium Type III contains enzymes from the European honeybee, the Gila monster and the Mexican beaded lizard.
Recently, we have completed studies to determine the myotoxic activity and the pathogenesis of myonecrosis induced by several of these enzymes isolated from various sources. Each enzyme was dissolved in physiologic saline (0.85% NaCl) to give the desired dose, then injected i.m. into CD- 1 white mice. At various times after injection, the mice were killed by an overdose of methoxyflurane, and a sample of skeletal muscle tissue was removed ,processed for microscopy and observed by light and electron microscopy.
Neither porcine pancreatic PLA2 (5.0µg/g) nor ß-bungarotoxin (0.01 and 0.07µg/g), both Type I PLA2s induced any detectable myonecrosis. However, several Type I PLA2s from Naja naja atra. Naja naja kaouthia, and Naja nigricollis venoms as well as scutoxinfrom Notechis scutatus scutatus venom. Two Type II myotoxins, i.e., ACL myotoxin from Agkistrodon contortrix laticinctus venom and CCV myotoxin from Crotalus viridis viridis venom, both induced myonecrosis. Also, one Type III PLA2, from honeybee (Apis mellifera) venom, induced myonecrosis in the same type of experiment.
The pathogenesis of myonecrosis induced by the myotoxic PLA2s regardless of Type was very similar. Early (first 3 hours) changes in the muscle cells are characterized by the presence of delta lesions, hypercontracted and clumped myofibrils and clear of cytoplasm. Electron microscopic examination of these types of cells indicates that the plasma membrane is ruptured in the area of the delta lesion and the cells are necrotic. Later changes (24 hours) are characterized by the presence of amorphous masses of disrupted myofilaments, macrophages in various stages of phagocytosis, absence of a plasma membrane, and an intact basal lamina. Differences in the strength and specificity of these myotoxins will be discussed in relation to their primary and secondary structures.
CORRESPONDENCE TO:
Dra. Charlotte L. Ownby - Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, 74078-0350, USA. email: carla@okway.okstate.edu
Publication Dates
-
Publication in this collection
08 Jan 1999 -
Date of issue
1997
