EDEMA FORMATION AND DEGRANULATION OF MAST-CELLS BY PHOSPHOLIPASE-A(2) PURIFIED FROM PORCINE PANCREAS AND SNAKE-VENOMS

Phospholipase A2 is ubiquitous in nature, with the highest concentrations occurring in pancreatic juice and in the venom of snakes. Local oedema formation is a common feature of the effects caused by snakebite, and indicates an increase in vascular permeability that could be produced by lipid mediators such as lysophospholipids, eicosanoids or PAF release by the enzymatic activity of PLA2. Desalted porcine pancreatic PLA2 exhibited strong oedema-inducing activity in a similar form to PLA2 venom from Naja naja or Crotalus durissus terrificus. Furthermore, all three PLA2s caused the release of histamine from rat peritoneal mast cells. However, non-desalted pancreatic PLA2 that was presented as an ammonium sulphate suspension (3.2 M) had no proinflammatory activity and clearly did not release histamine in vitro. When the enzymatic activity of PLA2 on mast cell membranes prelabelled with [H-3] arachidonic acid was determined, a relationship between the enzymatic activity and mast cell degranulation and the minimum oedema dose was observed. However, non-desalted porcine pancreatic PLA2 had the same enzymatic activity as the desalted enzyme but had little proinflammatory activity. This may be due to decreased histamine secretion caused by the presence of ammonium sulphate. Our study supports the idea that the proinflammatory activity of extracellular phospholipases could depend on their ability to cause mast cell degranulation. Moreover, the biological effects of PLA2 are correlated with the specific activities of the enzymes.