In Vitro Responses of Human Neutrophils to N-Formyl-Methionyl-Leucyl-Phenylalanine: Correlation with Effects of Acute Bacterial Infection

Abstract

In vitro responses of normal human neutrophils to N-formyl-methionyl-leucyl-phenylalanine (FMLP), the synthetic analog of a bacterial product, were correlated with the effects of acute bacterial infection on human neutrophils. The following perturbations In cellular functions that occurred in neutrophils obtained from patients with acute bacterial infection were mimicked in normal neutrophils pretreated with FMLP: (1) increased production of superoxide ion, as estimated by histochemical reduction of nitroblue tetrazolium (NBT); (2) increased rates of oxidative metabolism during phagocytosis of a heparin-NBT complex, latex, and opsonized zymosan; (3) enhanced response to a chemotactic stimulus, C5a; (4) increased degranulation and vacuolization of cytoplasm with neutral red supravital dye as the indicator; and (5) increased rate of membrane transport of 14C-Iabeled 2-deoxyglucose. Toxic granulation and elevated levels of alkaline phosphatase, which occurred in neutrophils from all of the patients with bacterial infection studied, could not be induced in control neutrophils that had been pretreated with FMLP. The results suggested that the mechanism of activation of neutrophils from many patients with acute bacterial infections could be an intravascular response to a biologically active material with properties similar to those of FMLP but that the elevated levels of alkaline phosphatase and the toxic granulation are due to different reactions.