Enhancement of human neutrophil bactericidal activity by chemotactic factors

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. We investigated whether chemotactic factors might also influence an event subsequent to chemotaxis, namely bacterial killing. It was found that preincubation (20 min at 37 degrees C) of human leukocytes with chemotactic substances such as zymosan-activated serum, a C5a-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. In addition, zymosan-activated serum, C5a fraction, and the two N-formyl methionyl peptides increased the hexose monophosphate shunt activity of resting and phagocytosing neutrophils by two- to threefold. In contrast, bacterial killing by sodium azide-treated neutrophils and neutrophils from a patient with chronic granulomatous disease was not increased by any chemotactic factor. These findings suggest that chemotactic factors stimulate neutrophil oxygen-dependent microbicidal pathways. These observations illustrate another important contribution of biologically active molecules to effector cell function and host defense.