SELECTIVE-INHIBITION BY PHENYTOIN OF CHEMOTACTIC FACTOR STIMULATED NEUTROPHIL FUNCTIONS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 103  (1) , 22-33
Abstract
Pretreatment of human neutrophils with phenytoin (0.05-0.8 mM) results in concentration-dependent, reversible inhibition of both superoxide anion generation and release of lysosomal enzymes (myeloperoxidase, lysozyme and .beta.-glucuronidase) provoked by either the synthetic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) or the complement fragment C5a. Phenytoin did not inhibit either enzyme release or superoxide anion generation by neutrophils stimulated with phorbol myristate acetate or serum-opsonized zymosan particles. Phenytoin did not provoke leakage from neutrophils of the cytoplasmic enzyme, lactate dehydrogenase, and did not inhibit directed migration (chemotaxis) of neutrophils toward either FMLP or C5a. Specific binding of 3H-FMLP to neutrophil membrane receptors was not altered significantly by pretreatment of the cells with a wide range of concentrations of phenytoin. With flow microfluorometry and the fluorochrome, 3,3''-dipentyloxacarbocyanine, phenytoin prevented FMLP-induced changes in fluorescence intensity (i.e., apparent neutrophil membrane depolarization). Various neutrophil functions may be regulated independently at other than the receptor level and neutrophil chemotactic responses to FMLP and C5a do not appear to be dependent on membrane events registered by 3,3''-dipentyloxacarbocyanine.