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

Murine membrane-bound phospholipase A receptor 1 (PLAR) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLAR. This study examined whether human soluble PLAR has biological functions and whether soluble PLAR exists in human plasma. Here, we showed that human recombinant soluble PLAR (rsPLAR) 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, rsPLAR 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 PLAR released from HEK293 cells transfected with a construct encoding human soluble PLAR. rsPLAR 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 rsPLAR with collagen-I. In addition, rsPLAR 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 PLAR. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLAR in human plasma. In conclusion, human recombinant soluble PLAR inhibits integrin β1-mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLAR in human plasma has the same properties as rsPLAR.