Histamine release from human leukocytes: studies with deuterium oxide, colchicine, and cytochalasin B

Abstract

Agents known to interact with either microtubules or microfilaments influenced the antigen-induced release of histamine from the leukocytes of allergic individuals. Deuterium oxide (D(2)O) which stabilizes microtubules and thereby favors their formation enhanced histamine release markedly. Concentrations as low as 5% increased antigen-induced release somewhat while concentrations as high as 75% had no effect on release in the absence of antigen. Enhancement occurred over a wide range of antigen concentrations and was also seen when release was initiated by antibody to IgE or IgG. When the release process was divided into two stages a D(2)O activity could be demonstrated only in the second stage. However, when D(2)O was present in the first stage together with agents which raise cyclic AMP levels and thereby inhibit release it partially reversed this inhibition. Colchicine, demecolcine, and vinblastine, compounds known to disaggregate microtubules, i.e., have an effect opposite to that of D(2)O, inhibited the release of histamine and counteracted the effects of D(2)O. The inhibitory action of colchicine was greater if cells were treated with colchicine before rather than after activation with antigen. Cytochalasin B, a compound which causes the disappearance of microfilaments, had variable effects on histamine release. The most frequently seen response was slight enhancement. Neither D(2)O nor cytochalasin B altered cyclic AMP levels in leukocytes. These observations support and strengthen the view that an intact and functioning microtubule system is directly important for the secretion of histamine from leukocytes and suggest that microfilaments might have multiple indirect effects.