The chemokine CXCL13 (BCA-1) inhibits FGF-2 effects on endothelial cells.
Several chemokines, belonging to both the CXC and CC classes, act as positive or negative regulators of angiogenesis. We sought to investigate the role of CXCL13, B cell-attracting chemokine 1 (BCA-1), also known as B-lymphocyte chemoattractant (BLC), on endothelial cell functions. We tested the effect of CXCL13 on HUVEC chemotaxis and proliferation in the presence of fibroblast growth factor (FGF)-2 and found that such chemokine inhibits FGF-2-induced 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 inhibits such rescue. Multiple mechanisms may be responsible for these biological activities as CXCL13 displaces FGF-2 binding to endothelial cells, inhibits FGF-2 homodimerization, and induces the formation of CXCL13-FGF-2 heterodimers. Our data suggest that CXCL13 may modulate angiogenesis by interfering with FGF-2 activity.
Spinetti
G
G
Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Istituto di Recovero e Cura a Carattere Scientifico, Rome 00167, Italy.
Camarda
G
G
Bernardini
G
G
Romano Di Peppe
S
S
Capogrossi
M C
MC
Napolitano
M
M
D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000494:pharmacology* / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects; D019281:Dimerization; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011485:Protein Binding; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism
C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D016222:Fibroblast Growth Factor 2