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-g amma-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 (B-max similar to 7.6 x 10(6) site s/cell) of moderate affinity (K-d approximate to 650 nM), The kinetics of PF-4 binding correlates with the proportion of PF-4 tetramers in s olution and with the activation of neutrophils for exocytosis. Reducti on of PF-4 binding and PF-4-induced exocytosis in the presence of vari ous glycosaminoglycans or following treatment of cells with chondroiti nase ABC (but not other glycosaminoglycan-degrading enzymes) altogethe r demonstrates that the PF-4 receptor is a proteoglycan off the chondr oitin sulfate class. Cross-linking experiments with radiolabeled PF-4 revealed a receptor-ligand complex of similar to 250 kDa, Taken togeth er, our data show that a distinct chondroitin sulfate proteoglycan rep resents specific receptors for tetrameric PF-4 on human neutrophils.