Secretory phospholipase A2 type IIA: a regulator of immune function in atherosclerosis?

Abstract

Soluble phospholipase A2 type IIA (sPLA2-IIA) is an acute-phase reactant that is markedly increased in inflammatory disorders including cardiovascular disease. Inflammatory cytokines such as interleukins IL-6 and IL-1β, interferon (IFN)-γ, and tumour necrosis factor (TNF)-α increase its expression in vascular smooth muscle cells and hepatocytes, two cell types largely responsible for its elevations in plasma. sPLA2-IIA is also highly expressed in atherosclerotic lesions and associated with smooth muscle cells, macrophages, and glycoaminoglycans,1 where it exerts proatherogenic effects in part by modifying low-and high-density lipoproteins (LDL and HDL). It hydrolyses the sn -2 ester bond in the glyceroacyl phospholipids present in both LDL and HDL and cell membranes, releasing fatty acids and lysophospholipids. sPLA2-IIA can also exert effects that are independent of its hydrolytic functions. It elevates IL-6 production by macrophages2 and contributes to elevations in cyclooxygenase-2 expression by mast cells:3 two cell types with significant roles in atherosclerosis. Thus, sPLA2-IIA is thought to promote atherosclerosis by hydrolysing lipoproteins and regulating macrophage and mast cell responses via non-hydrolytic mechanisms. In this issue of Cardiovascular Research , Ibeas et al. 4 provide additional new and somewhat unexpected insights as to how … *Corresponding author. Tel: +61 3 8532 1190; fax: 61 3 8532 1100. E-mail address : alex.bobik{at}bakeridi.edu.au