A chondroitin sulfate proteoglycan on human neutrophils specifically binds platelet factor 4 and is involved in cell activation.
Platelet factor 4 (PF-4), a member of the alpha-chemokine subfamily of cytokines, activates human neutrophils independently of intracellular free calcium mobilization or binding to IL-8R. In the present study, we have identified and partially characterized a receptor for PF-4 on human neutrophils, which displays weak cross-reactivity with the IFN-gamma-inducible protein 10, but not with other alpha-chemokines such as IL-8, neutrophil-activating peptide 2, or melanoma growth-stimulatory activity (GRO alpha). Binding studies revealed that human neutrophils express a high number of receptors (Bmax approximately 7.6 x 10(6) sites/cell) of moderate affinity (Kd approximately 650 nM). The kinetics of PF-4-binding correlates with the proportion of PF-4 tetramers in solution and with the activation of neutrophils for exocytosis. Reduction of PF-4 binding and PF-4-induced exocytosis in the presence of various glycosaminoglycans or following treatment of cells with chondroitinase ABC (but not other glycosaminoglycan-degrading enzymes) altogether demonstrates that the PF-4 receptor is a proteoglycan of the chondroitin sulfate class. Cross-linking experiments with radiolabeled PF-4 revealed a receptor-ligand complex of approximately 250 kDa. Taken together, our data show that a distinct chondroitin sulfate proteoglycan represents specific receptors for tetrameric PF-4 on human neutrophils.
Department of Immunology and Cell Biology, Research Center Borstel, Germany.
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Petersen
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Bock
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Flad
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Brandt
D002478:Cells, Cultured; D002809:Chondroitin Sulfates; D006801:Humans; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010978:Platelet Factor 4 / Q000276:immunology / Q000378:metabolism*; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
D011509:Proteoglycans; D019707:Receptors, Chemokine; D010978:Platelet Factor 4; D002809:Chondroitin Sulfates