Anti-inflammatory roles of secreted group V phospholipase A2

Resumen del póster presentado presentado al CIBERDEM Annual Meeting, celebrado en Cerdanyola del Vallès, Barcelona (España) del 11 al 13 de mayo de 2016.Diabetes Mellitus type 2 and atherosclerosis are closely related diseases. Dyslipidemia, inflammation and hyperglucemia, key features of diabetes disease, are all well-known causes of atherosclerosis. Macrophages can be divided into two different subsets: classically-activated macrophages, induced by interferon-g plus lipopolysaccharide, (M1), and alternatively-activated macrophages, induced by interleukin-4, (M2). These macrophages have been described in vivo in atherosclerotic lesions. M1 have been shown to promote the progression of atherosclerosis, and are more abundant within lesions of progressing plaques. M2 are characteristic of regressing atherosclerotic plaques. Macrophages constitute a major source of extracellular phospholipase A2, a family of enzymes with a significant role in atherosclerosis. sPLA2-V is involved in the establishment and progression of atherosclerotic plaques, and the regulation of immunoinflammatory response mounted by the macrophages. sPLA2-V hydrolyzes choline phospholipids on the surface of VLDL and LDL particles and leads to structural changes that diminish clearance of the lipoproteins, thereby increasing their residence time in the circulation and susceptibility to chemical modification. We sought to determine the actions of sPLA2-V on macrophages and key contributors to the chronic inflammatory state that is characteristic of the plaque. We show that in human monocyte-derived macrophages sPLA2-V is strongly upregulated by IL-4 but not by IFNg plus LPS. Hence, sPLA2-V constitutes a marker for human alternatively activated macrophages. Further, we show that the increased expression of sPLA2-V in IL-4-treated macrophages serves to regulate the cellular levels of ethanolamine phospholipids (LPE) that are necessary to support the elevated phagocytic response that these cells exhibit. Our results suggest that, in human atherosclerosis lesions, sPLA2-V could function as a bifaceted enzyme, augmenting the atherogenicity of LDL particles, but, also accelerating clearance of debris and thus reducing inflammation.Peer reviewe