The soluble D2D3(88-274) fragment of the urokinase receptor inhibits monocyte chemotaxis and integrin-dependent cell adhesion.
We have previously shown that chymotrypsin-cleaved soluble uPAR (D2D3(88-274)) elicits migration of monocytic cells through interaction with FPRL-1, a G protein-coupled receptor that is homologous to the fMLP receptor. Here, we report that D2D3(88-274) also modulates the ability of monocytes to migrate in response to other chemokines. Pretreatment of monocytes with increasing amounts of D2D3(88-274) prevents cell migration in response to MCP-1, RANTES and fMLP. We demonstrate that D2D3(88-274) does not inhibit MCP-1 receptor binding, elicit CCR2 internalization and prevent MCP-1-induced intracellular Ca(2+) increase. Thus, CCR2 receptor desensitization cannot account for D2D3(88-274)- mediated inhibition of MCP-1-induced cell migration. Rather, we show that pretreatment of monocytes with D2D3(88-274) dramatically decreases chemokine- induced integrin-dependent rapid cell adhesion by interacting with FPRL-1. Together, our results indicate that chemokine-dependent cell migration can be regulated not only by homologous and heterologous receptor desensitization, but also by inhibition of integrin-dependent cell adhesion, an important step in cell transmigration.[1]References
- The soluble D2D3(88-274) fragment of the urokinase receptor inhibits monocyte chemotaxis and integrin-dependent cell adhesion. Furlan, F., Orlando, S., Laudanna, C., Resnati, M., Basso, V., Blasi, F., Mondino, A. J. Cell. Sci. (2004) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
