Abstract
Synthetic formyl methionyl chemotactic peptides induce the various manifestations ofthe respiratory burst: increased 02 consumption, activation of the hexose mono-phosphate shunt, and increased production of superoxide (02-) and H202. They do soalone but to a much greater extent when in the presence of cytochalasin B. Superoxidegeneration by the chemotactic peptides in the presence of cytochalasin B shows thesame relationship of structure to activity as does the stimulation of chemokinesis andchemotaxis, granule enzyme secretion, and neutrophil aggregation by these sameagents. Carbobenzoxy-phenylalanyl-methionine, CBZ-Phe-Met, competitively inhibitsthe induced stimulation of locomotion, granule enzyme secretion, and neutrophilaggregation caused by the synthetic peptides. It also is a competitive inhibitor of O2- generation by the same peptides. The structure-activity and the competitive inhibitor studies lead to the conclusion that in polymorphonuclear leukocytes the chemotactic peptides induce superoxide formation and presumably the other manifestations of the respiratory burst by interacting with the same membrane receptor responsible for the stimulation of chemokinesis, chemotaxis, granule enzyme secretion, and neutrophil aggregation. The effectiveness of formyl-methionyl-leucyl-phenylalanine, F-Met-Leu-Phe, in generating 02- is greatly reduced but not abolished by removing calcium from the external medium. The calcium ionophore A23187 induces 02- generation that requires external calcium and is greatly enhanced by cytochalasin B. From these findings we hypothesize that the proximate cause of the induction of 02- formation and other manifestations of the respiratory burst by the chemotactic peptides is the influx into the neutrophil of Ca2+ and/or possibly Na+ previously shown to be induced by the peptides.
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