Phospholipase A2 inhibitor from Crotalus durissus terrificusrattlesnake: effects on human peripheral blood mononuclear cells andhuman neutrophils cells

Abstract

Crotalus Neutralizing Factor (CNF) is an inhibitor of phospholipase A2(PLA2), present in the blood plasmaof Crotalus durissus terrificus snake. This inhibitor neutralizes the lethal and enzymatic activity of crotoxin,the main neurotoxin from this venom. In this study, we investigated the effects of CNF on the functionalityof human peripheral blood mononuclear cells (PBMCs) and human neutrophils. The following parameterswere evaluated: viability and proliferation, chemotaxis, cytokines and LTB4production, cytosolic PLA2sactivity, myeloperoxidase (MPO) and superoxide anion (O2−) production. CNF showed no toxicity onPBMCs or neutrophils, and acts by stimulating the release of TNF- and LTB4, but neither stimulates IL-10 and IL-2 nor affects PBMCs proliferation and O2−release. In neutrophils, CNF induces chemotaxis butdoes not induce the release of both MPO and O2−. However, it induces LTB4and IL-8 production. Thesedata show the influence of CNF on PBMCs’ function by inducing TNF- and LTB4production, and onneutrophils, by stimulating chemotaxis and LTB4production, via cytosolic PLA2activity, and IL-8 release.The inflammatory profile produced by CNF is shown for the first time. Our present results suggest thatCNF has a role in activation of leukocytes and exert proinflammatory effects on these cell.