The chemokine CXCL13 (BCA-1) inhibits FGF-2 effects on endothelial cells

Several chemokines, belonging to both the CXC and CC classes, act as positi ve or negative regulators of angiogenesis. We sought to investigate the rol e of CXCL13, B cell-attracting chemokine 1 (BCA-1), also known as B-lymphoc yte chemoattractant (BLC), on endothelial cell functions. We tested the eff ect of CXCL13 on HUVEC chemotaxis and proliferation in the presence of fibr oblast growth factor (FGF)-2 and found that such chemokine inhibits FGF-2-i nduced functions, while is not active by itself. To test whether other FGF- 2-mediated biological activities may be affected, we evaluated the ability of CXCL13 to rescue HUVEC from starvation-induced apoptosis, as FGF-2 is a survival factor for endothelial cells, and found that CXCL13 partially inhi bits such rescue. Multiple mechanisms may be responsible for these biologic al activities as CXCL13 displaces FGF-2 binding to endothelial cells, inhib its FGF-2 homodimerization, and induces the formation of CXCL13-FGF-2 heter odimers. Our data suggest that CXCL13 may modulate angiogenesis by interfer ing with FGF-2 activity. (C) 2001 Academic Press.