Published online before print September 30, 2004, doi: 10.1161/01.RES.0000146674.38319.07
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Submitted on August 20, 2004
Revised on September 8, 2004
Accepted on September 21, 2004
Platelets Release CXCL4L1, a Nonallelic Variant of the Chemokine Platelet Factor-4/CXCL4 and Potent Inhibitor of Angiogenesis
Sofie Struyf ;
From the Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Belgium and Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles.
* To whom correspondence should be addressed. E-mail: jozef.vandamme{at}rega.kuleuven.ac.be.
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 bound heparin with lower affinity than CXCL4 but was more potent in inhibiting chemotaxis of human microvascular endothelial cells toward interleukin-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.
Key words: angiogenesis • endothelial cells • CXCL8/IL-8 • chemokines
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