Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro. Reduction of lysosomal enzyme release and superoxide anion production.

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Abstract
Cationic local anesthetics were reported to influence cellular responses to surface stimuli by interfering with function of microtubules and microfilaments. Since unimpaired microtubule and microfilament functions are required by human polymorphonuclear leukocytes in order to respond normally to surface stimulation the effects of the local anesthetic, tetracaine on the function and morphology of these cells in vitro were studied. Tetracaine (0.25-1.0 mM) significantly reduced extracellular release of lysosomal enzymes, .beta.-glucoronidase and lysozyme from polymorphonuclear leukocytes exposed to serum-treated zymosan (a particulate stimulus), zymosan-treated serum (a soluble stimulus) and to the surface-active lectin, concanavalin A. Tetracaine significantly reduced superoxide anion production (superoxide dismutase-inhibitable cytochrome reduction by these cells. Tetracaine was not cytotoxic, and its effects could be reversed completely by washing cells once with buffer. EM examination of tetracaine-treated cells revealed marked alterations of surface membranes. Microtubules and microfilaments appeared normal in resting polymorphonuclear leukocytes, but the increase in microtubules normally observed in stimulated cells was not seen after tetracaine treatment. Tetracaine probably interferes with those interactions between immune reactants and the polymorphonuclear leukocyte cell surface which provoke exocytosis and increased oxidative metabolism.