Human soluble phospholipase A 2 receptor is an inhibitor of the integrin-mediated cell migratory response to collagen-I.

Murine membrane-bound phospholipase A2 receptor 1 (PLA2 R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA2 R. This study examined whether human soluble PLA2 R has biological functions and whether soluble PLA2 R exists in human plasma. Here, we showed that human recombinant soluble PLA2 R (rsPLA2 R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin β1 on the cell surface of human embryonic kidney 293 (HEK293) cells. As a result, rsPLA2 R suppressed integrin β1-mediated migratory responses of HEK293 cells to collagen-I in Boyden chamber experiments. Inhibition of phosphorylation of FAK Tyr397 was also observed. Similar results were obtained with experiments using soluble PLA2 R released from HEK293 cells transfected with a construct encoding human soluble PLA2 R. rsPLA2 R lacking the fibronectin-like type II (FNII) domain had no inhibitory effects on cell responses to collagen-I, suggesting an important role of the FNII domain in the interaction of rsPLA2 R with collagen-I. In addition, rsPLA2 R suppressed the migratory response to collagen-IV and binding of collagen-IV to the cell surface of human podocytes that endogenously express membrane-bound, full-length PLA2 R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA2 R in human plasma. In conclusion, human recombinant soluble PLA2 R inhibits integrin β1-mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA2 R in human plasma has the same properties as rsPLA2 R.