The soluble D2D388-274 fragment of the urokinase receptor inhibits monocyte chemotaxis and integrin-dependent cell adhesion

• DOI: 10.1242/jcs.01149
• Publication Date: 2004-06-08T00:18:15Z
• Authors: Federico Furlan; Simone Orlando; Carlo Laudanna; Massimo Resnati; Veronica Basso; Francesco Blasi; Anna Mondino
• Keywords: Monocyte; Fragment (logic)

We have previously shown that chymotrypsin-cleaved soluble uPAR (D2D388-274) elicits migration of monocytic cells through interaction with FPRL-1, a G protein-coupled receptor is homologous to the fMLP receptor. Here, we report D2D388-274 also modulates ability monocytes migrate in response other chemokines. Pretreatment increasing amounts prevents cell MCP-1, RANTES and fMLP. demonstrate does not inhibit MCP-1 binding, elicit CCR2 internalization prevent MCP-1-induced intracellular Ca2+ increase. Thus, desensitization cannot account for D2D388-274-mediated inhibition migration. Rather, show pretreatment dramatically decreases chemokine-induced integrin-dependent rapid adhesion by interacting FPRL-1. Together, our results indicate chemokine-dependent can be regulated only heterologous desensitization, but adhesion, an important step transmigration.