SECRETORY GROUP-II PHOSPHOLIPASE-A2 IN HUMAN ATHEROSCLEROTIC PLAQUES

Atherosclerotic plaques exhibit a series of features that are similar to those of chronic inflammation. Based on the fact that during inflam mation several cell types synthesize and secrete a group II phospholip ase A2 (PLA2), an immunohistochemical study was undertaken to explore whether this enzyme can be identified in human atherosclerotic lesions . Tissue specimens obtained from 13 patients who had undergone arterie ctomy and three specimens with advanced atherosclerotic plaques obtain ed at autopsy were analyzed and compared to arteries free of atheroscl erosis. The results showed that in all areas with atherosclerotic lesi ons, a staining with monoclonal antibodies raised against group II PLA 2 was evident. In normal arteries without thickened intima, this immun ostaining was completely negative. With the use of specific monoclonal antibodies against macrophages (anti-KP-1) and smooth muscle cells (a nti-alpha-actin), PLA2-positive cells were identified as foam cells ma inly derived from macrophages. In addition to these cells, other regio ns of the thickened intima gave a partially positive reaction with ant i-PLA2 antibodies, but could not be stained with either anti-KP-1 or a nti-alpha-actin. Some of these regions were localized on edges of calc ification and cell necrosis. Other PLA2-positive regions seem to be as sociated with extracellular matrix structures. In summary, the finding s of this study may be regarded as further evidence to support the lin k between atherosclerosis and chronic inflammatory processes. In view of the fact that the in vitro modification of lipoproteins by PLA2-tre atment induces lipid deposition in macrophages, the results of this st udy suggest that group II PLA2 may actively be involved in the formati on of foam cells in vivo.