Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis

Circ Res. 2004 Oct 29;95(9):855-7. doi: 10.1161/01.RES.0000146674.38319.07. Epub 2004 Sep 30.

Abstract

Platelet factor-4 (PF-4)/CXCL4 was the first chemokine described to inhibit neovascularization. Here, the product of the nonallelic variant gene of CXCL4, PF-4var1/PF-4alt, designated CXCL4L1, was isolated for the first time from thrombin-stimulated human platelets and purified to homogeneity. Although secreted CXCL4 and CXCL4L1 differ in only three amino acids, CXCL4L1 was more potent in inhibiting chemotaxis of human microvascular endothelial cells toward interleukin-8 (IL-8)/CXCL8 or basic fibroblast growth factor (bFGF). In vivo, CXCL4L1 was also more effective than CXCL4 in inhibiting bFGF-induced angiogenesis in rat corneas. Thus, activated platelets release CXCL4L1, a potent regulator of endothelial cell biology, which affects angiogenesis and vascular diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Angiostatic Proteins / genetics
  • Angiostatic Proteins / isolation & purification
  • Angiostatic Proteins / metabolism*
  • Angiostatic Proteins / pharmacology
  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Cells, Cultured / drug effects
  • Cells, Cultured / physiology
  • Chemotaxis / drug effects
  • Corneal Neovascularization / chemically induced
  • Culture Media, Conditioned / pharmacology
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Endothelium, Vascular / cytology
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblast Growth Factor 2 / antagonists & inhibitors
  • Fibroblast Growth Factor 2 / pharmacology
  • Humans
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / pharmacology
  • Molecular Sequence Data
  • Platelet Activation
  • Platelet Factor 4 / genetics
  • Platelet Factor 4 / isolation & purification
  • Platelet Factor 4 / metabolism*
  • Platelet Factor 4 / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Thrombin / pharmacology

Substances

  • Angiostatic Proteins
  • Culture Media, Conditioned
  • Interleukin-8
  • PF4V1 protein, human
  • Fibroblast Growth Factor 2
  • Platelet Factor 4
  • Thrombin