INSULIN-LIKE GROWTH-FACTORS ENHANCE PHAGOCYTOSIS BY HUMAN NEUTROPHILSIN-VITRO

Polymorphonuclear neutrophils (PMNs) were isolated from human blood, a nd PMN phagocytosis was assessed by measuring the chemiluminescence (C L) response in the presence of ZAP (opsonized zymosin particles contai ning luminol). The administration of 6.5 nM of insulin-like growth fac tor I(IGF-I), des(1-3)-IGF-I, IGF-II or insulin to PMNs for 20 min res ulted in significant increases of the CL response for all test prepara tions rations. Des(l-3)-IGF-I, a truncated IGF-I with low affinity bin ding to IGF binding proteins (IGFBPs), was the most potent CL stimulat or. The CL production evoked by 6.5 nM of des(1-3)-IGF-I was inhibited significantly by both 0.25 and 1.0 mM of EGTA (Ca2+ chelator), or 10 mu M nifedipine (Ca2+ channel inhibitor), pertussis toxin (0.05 and 1. 0 mu g/ml) or cholera toxin (5 mu g/ml). These results suggest that IG F-I and its homologues are potent stimulators of phagocytosis and that this action is modulated by IGFBP, and may require extracellular Ca2 and/or IGF-I receptor G-protein coupling.