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

Biochem Biophys Res Commun. 2001 Nov 23;289(1):19-24. doi: 10.1006/bbrc.2001.5924.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • B-Lymphocytes / immunology
  • Cell Division / drug effects
  • Cells, Cultured
  • Chemokine CXCL13
  • Chemokines, CXC / pharmacology*
  • Chemokines, CXC / physiology
  • Chemotaxis / drug effects
  • Dimerization
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Fibroblast Growth Factor 2 / antagonists & inhibitors*
  • Fibroblast Growth Factor 2 / chemistry
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Humans
  • Neovascularization, Physiologic / drug effects
  • Protein Binding
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine / metabolism

Substances

  • CXCL13 protein, human
  • CXCR5 protein, human
  • Chemokine CXCL13
  • Chemokines, CXC
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Fibroblast Growth Factor 2