Human soluble phospholipase A2 receptor is an inhibitor of the integrin-mediated cell migratory response to collagen-I

Murine membrane-bound phospholipase A(2) receptor 1 (PLA(2)R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA(2)R. This study examined whether human soluble PLA(2)R has biological functions and whether soluble PLA2R exists in human plasma. Here, we showed that human recombinant soluble PLA(2)R (rsPLA(2)R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin beta 1 on the cell surface of human embryonic kidney 293 (HEK293) cells. As a result, rsPLA(2)R suppressed integrin beta 1-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 PLA(2)R released from HEK293 cells transfected with a construct encoding human soluble PLA(2)R. rsPLA(2)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 rsPLA(2)R with collagen-I. In addition, rsPLA(2)R suppressed the migratory response to collagen-IV and binding of collagen-IV to the cell surface of human podocytes that endogenously express membranebound, full-length PLA(2)R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA(2)R in human plasma. In conclusion, human recombinant soluble PLA(2)R inhibits integrin beta 1-mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA(2)R in human plasma has the same properties as rsPLA(2)R.