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

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.