The Mechanism of Action of Soluble Lymphocyte Mediators

Abstract

The effect of migration inhibitory factor (MIF) on macrophage microtubules was examined by functional, biochemical and morphological methods. It was found that: (1) the microtubule-stabilizing agent deuterium oxide (D2O) inhibits spontaneous macrophage migration from capillaries and enhances the migration blocking effect of MIF; (2) MIF does not modify the amount of total tubulin in macrophages, as determined by an 3H-colchicine binding assay, but increases significantly the proportion of tubulin present in polymeric form; (3) macrophages exposed to MIF and examined by immunofluorescence with specific antitubulin antibody demonstrate a striking increase in the percentage of cells with a well-organized microtubular network, characterized by a high density of thick fibrils and prominent paranuclear micro tubule organizing centers. It is concluded that MIF inhibits cellular motility by inducing the formation of numerous microtubules, probably by enhancing tubulin polymerization.