Biological effects of secretory phospholipase A(2) group IIA on lipoproteins and in atherogenesis.
Secretory phospholipase A(2) group IIA(sPLA(2) IIA) can be produced and secreted by various cell types either constitutionally or as an acute-phase reactant upon stimulation by proinflammatory cytokines. The enzyme prefers phosphatidylethanolamine and phosphatidylserine as substrates. One important biological function may be the hydrolytic destruction of bacterial membranes. It has been demonstrated, however, that sPLA(2) can also hydrolyse the phospholipid monolayers of high density lipoprotein (HDL) and low density lipoprotein (LDL) in vitro. Secretory phospholipase A(2)-modified LDL show increased affinity to glycosaminoglycans and proteoglycans, a tendency to aggregate, and an enhanced ability to deliver cholesterol to cells. Incubation of cultured macrophages with PLA(2)-treated LDL and HDL is associated with increased intracellular lipid accumulation, resulting in the formation of foam cells. Elevated sPLA(2)(IIA) activity in blood serum leads to an increased clearance of serum cholesterol. Secretory phospholipase A(2)(IIA) can also be detected in the intima, adventitia and media of the atherosclerotic wall not only in developed lesions but also in very early stages of atherosclerosis. The presence of DNA of Chlamydia pneumoniae, herpes simplex virus, and cytomegalovirus was found to be associated with sPLA(2)(IIA) expression and other signs of local inflammation. Thus, sPLA(2)(IIA) appears to be one important link between the lipid and the inflammation hypothesis of atherosclerosis.
Jaross
Werner
W
Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technical University of Dresden, Germany. Jaross@rcs.urz.tu-dresden.de
Eckey
Rolf
R
Menschikowski
Mario
M
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D054501:Group II Phospholipases A2; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D010741:Phospholipases A / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
D006025:Glycosaminoglycans; D008074:Lipoproteins; D010743:Phospholipids; D011509:Proteoglycans; D010741:Phospholipases A; D054501:Group II Phospholipases A2