SUPEROXIDE PRODUCTION INDUCED IN RABBIT POLYMORPHONUCLEAR LEUKOCYTES BY SYNTHETIC CHEMOTACTIC PEPTIDES AND A23187 - NATURE OF THE RECEPTOR AND THE REQUIREMENT FOR CA2+

  • 1 January 1979
    • journal article
    • research article
    • Vol. 95  (1) , 81-97
Abstract
Synthetic formyl methionyl chemotactic peptides induce the various manifestations of the respiratory burst: increased O2 consumption, activation of the hexose monophosphate shunt and increased production of superoxide (O2-) and H2O2. They do so to a much greater extent when in the presence of cytochalasin B. Superoxide generation by the chemotactic peptides in the presence of cytochalasin B shows the same relationship of structure to activity as does the stimulation of chemokinesis and chemotaxis, granule enzyme secretion and neutrophil aggregation by these same agents. Carbobenzoxy-phenylalanyl-methionine, CBZ-Phe-Met, competitively inhibits the induced stimulation of locomotion, granule enzyme secretion and neutrophil aggregation 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 O2- is greatly reduced but not abolished by removing Ca from the external medium. The Ca ionophore A23187 induces O2- generation that requires external Ca and is greatly enhanced by cytochalasin B. The proximate cause of the induction of O2- formation and other manifestations of the respiratory burst by the chemotactic peptides is apparently the influx into the neutrophil of Ca2+ and/or possibly Na+ previously shown to be induced by the peptides.