Inflammatory Effects of Phospholipases A: Mechanisms Involved in Biosynthesis of Lipid Mediators and Lipid Accumulation.

Phospholipases As (PLAs) constitute one of the major protein groups present in the venoms of viperid and crotalid snakes. Snake venom PLAs (svPLAs) exhibit a remarkable functional diversity, as they have been described to induce a myriad of toxic effects. Local inflammation is an important characteristic of snakebite envenomation inflicted by viperid and crotalid species and diverse svPLAs have been studied for their proinflammatory properties. Moreover, based on their molecular, structural, and functional properties, the viperid svPLAs are classified into the group IIA secreted PLAs, which encompasses mammalian inflammatory sPLAs. Thus, research on svPLAs has attained paramount importance for better understanding the role of this class of enzymes in snake envenomation and the participation of GIIA sPLAs in pathophysiological conditions and for the development of new therapeutic agents. In this review, we highlight studies that have identified the inflammatory activities of svPLAs, in particular, those from genus snakes, which are major medically important snakes in Latin America, and we describe recent advances in our collective understanding of the mechanisms underlying their inflammatory effects. We also discuss studies that dissect the action of these venom enzymes in inflammatory cells focusing on molecular mechanisms and signaling pathways involved in the biosynthesis of lipid mediators and lipid accumulation in immunocompetent cells.