Chemotactic factors trigger their own oxidative inactivation by human neutrophils

Human neutrophils exposed to phagocytosable particles or soluble activating agents are able to inactivate chemotactic factors. The present experiments demonstrate that the peptide chemoattractant, f-met-leu-phe, serves as a sufficient secretory stimulus to trigger its own functional inactivation by neutrophils. This phenomenon is dependent on the concentration of the chemoattractant and the duration of its exposure to neutrophils. It requires low numbers of viable neutrophils and physiologic concentrations of chloride and is blocked by addition of azide, cyanide, catalase, or methionine, but not methionine sulfoxide, superoxide dismutase, or heated catalase. Neutrophils from patients with myeloperoxidase deficiency of chronic granulomatous disease are not able to inactivate the chemotactic factor unless purified myeloperoxidase or hydrogen peroxide, respectively, is added. Thus, chemotactic peptides can trigger neutrophils to secrete myeloperoxidase and hydrogen peroxide, which together with a halide destroy the biologic activity of the peptide, probably by oxidizing a methionine residue. These observations support the pathophysiologic significance of oxidative inactivation of humoral mediators as a negative feedback inflammatory control mechanism.