Secreted phospholipase A(2) induces vascular endothelial cell migration

Secreted phospholipase Ap (SPLA(2)) regulates a Variety of cellular functio ns. The present investigation was undertaken to elucidate the potential rol e of sPLA(2) in endothelial cell (EC) migration. Bovine aortic endothelial cells (BAECs) exposed to sPLA(2) placed in the lower compartment of a modif ied Boyden chamber displayed increased migration compared to cells exposed to vehicle. The effect of sPLA(2) on EC migration was time and dose depende nt. Migration of BAECs was observed at 30 minutes, increased over 1 to 2 ho urs, and declined thereafter. At 2 hours of stimulation, sPLA2 (0.01-2 mu m ol/L) induced 1.2- to 3-fold increased cell migration compared with media a lone. Among the different sPLA(2)s tested, bee venom, Naja naja, and porcin e and human pancreatic PLA(2)s all evoked a migratory response in ECs, More over, human synovial fluid, obtained from patients with arthritis and conta ining sPLA(2) activity, induced EC migration. Migration of ECs was signific antly reduced after exposure to a catalytic site mutant of pancreatic sPLA( 2) with decreased lipolytic activity as compared to wild-type sPLA(2), Simi larly, pretreatment of human synovial fluid with p-bromophenacyl bromide, a n irreversible inhibitor of sPLA(2), markedly decreased the ability of huma n synovial fluid to stimulate EC migration. Moreover, migration of ECs was stimulated on exposure to hydrolytic products of sPLA(2) activity including arachidonic acid, lysophosphatidic acid, and lysophosphatidylcholine. Thes e findings suggest that sPLA(2) plays a physiologic role in induction of EC migration. Moreover, the effects of sPLA(2) on EC migration are mediated, at least in part, by its catalytic activity. (C) 2000 by The American Socie ty of Hematology.