Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis.
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.
Struyf
Sofie
S
Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Burdick
Marie D
MD
Proost
Paul
P
Van Damme
Jo
J
Strieter
Robert M
RM
D000483:Alleles; D000595:Amino Acid Sequence; D043165:Angiostatic Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects; D016510:Corneal Neovascularization / Q000139:chemically induced; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008969:Molecular Sequence Data; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology
D043165:Angiostatic Proteins; D017077:Culture Media, Conditioned; D016209:Interleukin-8; C064936:PF4V1 protein, human; D016222:Fibroblast Growth Factor 2; D010978:Platelet Factor 4; D013917:Thrombin