INHIBITION OF FC-GAMMA-R-DEPENDENT FUNCTIONS BY N-FORMYLMETHIONYLLEUCYLPHENYLALANINE IN HUMAN NEUTROPHILS

Human polymorphonuclear neutrophils (PMN) participate in different cel lular functions, including phagocytosis, antibody-dependent cell-media ted cytotoxicity (ADCC), and release of reactive oxygen intermediates. Each of these functions can be triggered by receptors for the Fc port ion of IgG molecules (Fc gamma R). Normal resting neutrophils possess Fc gamma RII and Fc gamma RIIIB receptors. They also have specific mem brane receptors for formylated peptides such as the prototype N-formyl methionylleucylphenylalanine (FMLP). In this report, we present eviden ce that preincubation of PMN with FMLP inhibits different PMN Fc gamma R-dependent functions such as phagocytosis, ADCC, and immune complex- dependent cytotoxicity. These inhibitory effects can be explained, at least in part, by downregulation of both Fc gamma RII, and Fc gamma RI II. Unexpectedly, preincubation of FMLP with PMN was not necessary for ADCC inhibition. Taking into account that the FMLP-dependent Fc gamma R downregulation is not observed before 30 min of incubation, and the onset of ADCC occurs rapidly (seconds), it is possible that FMLP can modify this function by altering early intracellular events. (C) 1997 Academic Press.