Neutrophil iodination reaction induced by fluoride: Implications for degranulation and metabolic activation

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8 Scopus citations

Abstract

Activation of neutrophils by phagocytosis or certain soluble stimuli results in a burst of oxidative metabolism and in degranulation. Fluoride is known to trigger the metabolic burst, but degranulation has not been reported. Iodination of protein by F--activated human PMN was demonstrated by measuring TCA-precipitable 125I. Iodination was dependent on H2O2, since it was inhibited by catalase, enhanced by superoxide dismutase, and absent in PMN from patients with chronic granulomatous disease. Dependence on myeloperoxidase was indicated by an inhibitory effect of azide and cyanide and by the absence of iodination in myeloperoxidase-deficient PMN. Soluble extracellular protein was the predominant substrate for iodination, suggesting secretion of myeloperoxidase and H2O2. Maximum iodination occurred after a 60-min exposure of PMN to 20-30 mM fluoride. At greater than 30 mM F-, there was a sharp decrease in iodination. Peak iodination was lower than with other PMN activators. These observations suggested an inhibitory effect of F- on iodination, especially at high concentrations. Indeed, F- at 20-30 mM caused >50% inhibition of iodination by PMN exposed to zymosan or phorbol myristate acetate. This may relate to suppression of glycolysis by F-, since two other glycolytic inhibitors, iodoacetamide and 2-deoxy-D-glucose, caused similar inhibition of iodination. Fluoride also inhibited O2 consumption and H2O2 formation by PMN. The results show that the net effect of F- activation of PMN represents a summation of two opposing processes: (1) stimulation of metabolic activation (H2O2 formation) and degranulation (myeloperoxidase secretion) and degranulation (myeloperoxidase secretion) and (2) inhibition of these events, probably by interference with glycolytic energy metabolism.

Original languageEnglish (US)
Pages (from-to)913-921
Number of pages9
JournalBlood
Volume57
Issue number5
DOIs
StatePublished - 1981
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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