Enhancement of Human Neutrophil Bactericidal Activity by Chemotactic Factors

Abstract

Neutrophils are important effector cells in the defense against microorganisms. They migrate into infected sites and then phagocytose and kill bacteria. Chemotactic factors may be important for initiating neutrophil migration. Chemotactic factors might influence an event subsequent to chemotaxis, namely bacterial killing. Pre-incubation (20 min at 37.degree. C) of human leukocytes with chemotactic substances such as zymosan-activated serum, a C5a[fragment a of complement component 5]-containing fraction of zymosan-activated serum, N-formyl methionyl phenylalanine or N-formyl methionyl-leucine-phenylalanine enhanced leukocyte killing of Staphylococcus aureus, Escherichia coli and Streptococcus faecalis in a dose-dependent fashion. The concentration of chemotactic factor required to enhance killing was similar to that required to induce neutrophil chemotaxis. Zymosan-activated serum, C5a fraction and the 2 N-formyl methionyl peptides increased the hexose monophosphate shunt activity of resting and phagocytosing neutrophils by 2- to 3-fold. Bacterial killing by sodium azide-treated neutrophils and neutrophils from a patient with chronic granulomatous disease was not increased by any chemotactic factor. Chemotactic factors may stimulate neutrophil O2-dependent microbicidal pathways. An important contribution of biologically active molecules to effector cell function and host defense is illustrated.