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(Circulation Research. 2004;95:855.)
© 2004 American Heart Association, Inc.

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Platelets Release CXCL4L1, a Nonallelic Variant of the Chemokine Platelet Factor-4/CXCL4 and Potent Inhibitor of Angiogenesis

Sofie Struyf, Marie D. Burdick, Paul Proost, Jo Van Damme, Robert M. Strieter

From the Laboratory of Molecular Immunology (S.S., P.P., J.V.D.), Rega Institute, University of Leuven, Belgium; and Division of Pulmonary and Critical Care Medicine (M.D.B., R.M.S.), David Geffen School of Medicine at University of California Los Angeles.

Correspondence to Jo Van Damme, Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail jozef.vandamme{at}rega.kuleuven.ac.be

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-4_var1/PF-4_alt, 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.

Key Words: angiogenesis • endothelial cells • CXCL8/IL-8 • chemokines

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