PLATELET-DERIVED GROWTH-FACTOR PROMOTES POLYMORPHONUCLEAR LEUKOCYTE ACTIVATION

Abstract

The platelet-derived growth factor (PDGF) has several well defined important biologic activities. PDGF is the major mitogen in human serum for cells of mesenchymal origins; it is a potent chemoattractant protein for human monocytes, neutrophils, fibroblasts and smooth muscle cells; and was implicated in transformation by simian sarcoma virus and perhaps in transformation by other agents as well. In this article, PDGF was shown to stimulate activation of human peripheral blood neutrophils defined by loss of membrane associated Ca as reflected by loss of chlortetracycline fluorescence, release of superoxide anion and specific granule enzymes, and enhanced neutrophil adherence and aggregation. These responses occurred in a dose-dependent fashion at concentrations of PDGF between 10 ng/ml (0.4 nmol/l) and 40 ng/ml (1.5 nmol/l) and were comparable to effects obtained with optimal concentrations of fMLP and C5a. Degranulation induced by PDGF was selective for secondary (specific) granules and not primary (azurophil) granules. PDGF thus is ideally suited for a pivotal role in attracting inflammatory cells locally and initiating neutrophil activation at sites of blood vessel injury. PDGF or a closely related protein also may play and important role in attracting and activating neutrophils in association with inflammatory tumors.