Platelet-derived growth factor stimulates phagocytosis and blocks agonist-induced activation of the neutrophil oxidative burst: a possible cellular mechanism to protect against oxygen radical damage.
The effect of platelet-derived growth factor (PDGF) on agonist-induced activation of the superoxide-generating oxidative burst in human neutrophils was tested. PDGF had no effect on the resting level of superoxide generation but inhibited both the rate and the extent of fMet-Leu-Phe-stimulated superoxide production in a dose-dependent manner. The concentration required to inhibit the response by 50% was 95 +/- 26 pM (n = 10). PDGF also blocked activation by other receptor-mediated agonists such as the complement protein C5a and opsonized zymosan, but not by phorbol myristate acetate or arachidonate, both of which may act at postreceptor sites. The growth factor, however, had no effect on the binding of fMet-Leu-Phe to its receptor. PDGF in concentrations that blocked the oxidative burst stimulated phagocytosis of opsonized latex particles. Thus, PDGF functions as a heterologous "down-regulator" of receptor-mediated activation of the neutrophil oxidative burst and an activator of phagocytosis. A model for a feedback regulatory loop between platelets and neutrophils is proposed.
D001792:Blood Platelets / Q000502:physiology; D005246:Feedback; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D013481:Superoxides / Q000097:blood*
D010982:Platelet-Derived Growth Factor; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine