Original Article

Lipoproteins are substrates for human secretory group IIA phospholipase A₂: preferential hydrolysis of acute phase HDL

Correspondence to: Waldemar Pruzanski.

Group IIA secretory phospholipase A₂ is an acute phase enzyme, co-expressed with serum amyloid A protein. Both are present in atherosclerotic lesions. We report that human normal and acute phase high density lipoproteins and low density lipoprotein are effective substrates for human group IIA phospholipase A₂. The enzyme hydrolyzed choline and ethanolamine glycerophospholipids at the sn -2 position resulting in an accumulation of the corresponding lysophospholipids, including the unhydrolyzed alkyl and alkenyl ether derivatives. The hydrolysis of acute phase high density lipoprotein was 2- to 3-fold more rapid and intensive than of normal high density lipoprotein. The hydrolysis of lipoproteins was noted at enzyme concentration as low as 0.05 µg/mg protein, which was within the range observed in the circulation in acute and chronic inflammatory diseases. The enzyme hydrolyzed the different molecular species of the residual glycerophospholipids in proportion to their mass, showing no preference for the release of arachidonic acid. Group IIA phospholipase A₂ preferentially attacked the hydroxy and hydroperoxy linoleates and possibly other oxygenated fatty acids, which were released from the glycerophospholipids at early times of incubation. There was no effect on the content or molecular species composition of the sphingomyelins or neutral lipids of the lipoproteins.

In conclusion, human plasma lipoproteins are the first reported natural biological substrates for human group IIA phospholipase A₂. The enhanced hydrolysis of acute phase high density lipoproteins is probably due to its association with serum amyloid A protein, which enhances the activity of the enzyme and may promote its penetration to the lipid monolayer. As sPLA₂-induced hydrolysis of the lipoproteins leads to accumulation of lysophosphatidylcholine and potentially toxic oxygenated fatty acids, overexpression of this enzyme may be proatherogenic.—Pruzanski, W., E. Stefanski, F. C. de Beer, M. C. de Beer, P. Vadas, A. Ravandi, and A. Kuksis. Lipoproteins are substrates for human secretory group IIA phospholipase A₂: preferential hydrolysis of acute phase HDL. J. Lipid. Res. 39: 2150–2160.

Supplementary key words: lipoproteins, group IIA phospholipase A ₂, hydrolysis, lysophosphatidylcholine, free fatty acids, atherosclerosis

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