Phospholipase A Inhibitor from Crotalus durissus terrificus rattlesnake: Effects on human peripheral blood mononuclear cells and human neutrophils cells.

Crotalus Neutralizing Factor (CNF) is an inhibitor of phospholipase A (PLA), present in the blood plasma of 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 functionality of human peripheral blood mononuclear cells (PBMCs) and human neutrophils. The following parameters were evaluated: viability and proliferation, chemotaxis, cytokines and LTB production, cytosolic PLAs activity, myeloperoxidase (MPO) and superoxide anion (O) production. CNF showed no toxicity on PBMCs or neutrophils, and acts by stimulating the release of TNF-α and LTB, but neither stimulates IL-10 and IL-2 nor affects PBMCs proliferation and O release. In neutrophils, CNF induces chemotaxis but does not induce the release of both MPO and O. However, it induces LTB and IL-8 production. These data show the influence of CNF on PBMCs' function by inducing TNF-α and LTB production, and on neutrophils, by stimulating chemotaxis and LTB production, via cytosolic PLA activity, and IL-8 release. The inflammatory profile produced by CNF is shown for the first time. Our present results suggest that CNF has a role in activation of leukocytes and exert proinflammatory effects on these cell.