THE FUNCTIONAL-ROLE OF THE ELR MOTIF IN CXC CHEMOKINE-MEDIATED ANGIOGENESIS

In this study, we demonstrate that the CXC family of chemokines displa ys disparate angiogenic activity depending upon the presence or absenc e of the ELR motif. CXC chemokines containing the ELR motif (ELR-CXC c hemokines) were found to be potent angiogenic factors, inducing both i n vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines lacking the ELR motif, platelet facto r 4, interferon gamma-inducible protein 10, and monokine induced by ga mma-interferon, not only failed to induce significant in vitro endothe lial cell chemotaxis or in vivo corneal neovacularization but were fou nd to be potent angiostatic factors in the presence of either ELR-CXC chemokines or the unrelated angiogenic factor, basic fibroblast growth factor, Additionally, mutant interleukin-g proteins lacking the ELR m otif demonstrated potent angiostatic effects in the presence of either ELR-CXC chemokines or basic fibroblast growth factor, In contrast, a mutant of monokine induced by gamma-interferon containing the ELR moti f was found to induce in vivo angiogenic activity, These findings sugg est a functional role of the ELR motif in determining the angiogenic o r angiostatic potential of CXC chemokines, supporting the hypothesis t hat the net biological balance between angiogenic and angiostatic CXC chemokines may play an important role in regulating overall angiogenes is.