Journal of Dental Research, Vol 65, 1159-1165, Copyright © 1986 by International & American Associations for Dental Research Online Journals
Modulation of the kinetics of induced neutrophil superoxide generation by fluoride
W. L. Gabler, H. R. Creamer and W. W. Bullock
Fluoride (F-) is unique in that, depending upon concentration, it can
either stimulate or inhibit the synthesis of the neutrophil's major
intracellular microbicidal product, superoxide anion (O2-). While a number
of studies have delved into F- induction of O2- generation, little has been
reported on the effect of F- on the synthesis of O2- induced by other
agents. In this report, we show that F- inhibits the activation and
activity of neutrophils induced either by
formyl-methionyl-leucylphenylalanine (FMLP) or by phorbol myristate acetate
(PMA). The extent of increase in lag period and decrease in velocity of O2-
synthesis was found to be directly related to the concentrations of F- and
of hydrogen ion in the medium and to the length of contact time between the
neutrophil and F-. Decreasing the pH of the medium, while maintaining a
constant concentration of F-, disproportionately increased the inhibitory
effect of the anion over the effect of pH alone. Fluoride inhibited the
responsiveness of neutrophils to FMLP more than it did their responsiveness
to PMA. A gradual but partial reversal of F-'s inhibition of O2- synthesis
could be achieved by transferring inhibited cells to F(-)-free medium. Our
study shows that the suppression of both FMLP- and PMA-induced synthesis of
O2- by neutrophils is most dramatic at a reduced pH and is probably related
to the intracellular accumulation of F-.(ABSTRACT TRUNCATED AT 250 WORDS)
