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The Effects of Extracellular K+, Na+ and Ca++ on Lysosomal Enzyme Secretion from Polymorphonuclear Leukocytes

1977; American Association of Immunologists; Volume: 119; Issue: 3 Linguagem: Inglês

10.4049/jimmunol.119.3.804

1550-6606

Henry J. Showell, Paul H. Naccache, R.I. Sha’afi, Elmer L. Becker,

Neonatal and fetal brain pathology

Abstract Release of the lysosomal enzymes, lysozyme and β-glucuronidase, from rabbit peritoneal polymorphonuclear leukocytes induced by three kinds of secretogogues, chemotactic factors in the presence of cytochalasin B, the K+ ionophore, valinomycin, and the Ca++ ionophore, A23187 is profoundly affected by the presence and level of K+, Na, and Ca++ in the extracellular medium. K+ approximately doubles the ability of all chemotactic factors to release in the presence of cytochalasin B. Ouabain, except in a minority of instances, does not prevent enhancement by K+ suggesting that the enhancement is not due to activation of the Na+,K+ pump. Other monovalent cations can substitute for K+ but with less efficiency. Removing Na+ from the medium increased spontaneous release in the presence of Ca++ but to a much lesser extent in its absence. Chemotactic factor-stimulated release is depressed in the absence of Na+. The K+ ionophore, valinomycin, has no effect on chemotactic factor-stimulated release; however, it is capable of inducing release by itself. The secretogogue action of valinomycin requires the presence of Ca++ and is enhanced by cytochalasin B or K+. Nigericin, another K+ ionophore, in noncytotoxic concentrations is without effect on release. The enhancing effect of Ca++ on release by chemotactic factors and cytochalasin B was confirmed. La+++ has two effects on release; at sufficiently low concentrations it inhibits the Ca++-dependent release induced by chemotactic factors. At concentrations above 10-5 M, it can sustain chemotactic factor-dependent release in the presence or absence of Ca++. The release induced by the Ca++ ionophore A23187 requires Ca++ and is enhanced by cytochalasin B and by K+. The results obtained attest to the central role of external Ca++ in the induced secretion of lysosomal enzymes from the neutrophil. It is suggested that all three kinds of secretogogues induce release by causing an influx of Ca++ into the cytoplasm of the PMN. Cytochalasin B and K+ are believed to exert their effects by increasing the rate or extent of the hypothesized Ca++ influx.