Ultrastructural Localization of Secretory Type II Phospholipase A₂ in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

From the Wallenberg Laboratory (M.R., E.R., E.H.-C.) and the Department of Pathology (S.B.), Göteborgs University, Göteborg 41 345, Sweden.

Abstract—We recently reported on the immunolocalization of type II secretory nonpancreatic phospholipase A₂ (snpPLA₂) in human atherosclerotic lesions. In the present study, we present data on the distribution and ultrastructural localization of snpPLA₂ in adjacent nonatherosclerotic and atherosclerotic regions of human arteries. Electron microscopy (EM) of immunogold labeling techniques with a monoclonal antibody was used to analyze arterial tissue. The human specimens analyzed were obtained from autopsy and surgery cases. The results with EM showed a stronger snpPLA₂ immunoreactivity in regions of arteries with atherosclerotic lesions than in regions without lesions from the same individual. snpPLA₂ immunoreactivity was stronger in the arterial intima of atherosclerotic than of nonatherosclerotic tissue. EM-immunogold examination revealed that the majority of snpPLA₂ was localized along the extracellular matrix, associated with collagen fibers and other extracellular matrix structures. Intracellular snpPLA₂ was observed in electron-dense vesicles in intimal cells. snpPLA₂ was also found in contact with large, extracellular lipid droplets. These results support the hypothesis that extracellular snpPLA₂ is localized at sites where it may hydrolyze phospholipids from lipoproteins and lipid aggregates retained in the extracellular matrix of the arterial wall. This may be a mechanism for in situ release of proinflammatory lipids, free fatty acids, and lysophosphatidylcholine in regions of apolipoprotein B accumulation, which are abundant in atherosclerotic lesions.

Key Words: atherosclerosis • inflammation • phospholipase A₂ • matrix

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