Mechanisms of Microtubule Disassembly in Vivo: Studies in Normal and Chronic Granulomatous Disease Leucocytes

Abstract

Microtubule assembly in human polymorphonuclear leukocytes is a dynamic process that can be initiated by binding of the plant lectin Concanavalin A [Con A] to surface receptors. Colchicine inhibits lectin-induced microtubule assembly and promotes the movement of Con A into surface caps. Inhibition of microtubule assembly and enhanced Con A cap formation also follow treatment of normal leukocytes with 2 specific glutathione-oxidizing agents, diamide and tertiary butylhydroperoxide. Exogenous H2O2 induces Con A capping on normal polymorphonuclear leukocytes but only at concentrations that simultaneously oxidize glutathione. Diamide and tertiary butylhydroperoxide cause Con A cap formation in leukocytes from patients with chronic granulomatous disease. These cells cannot generate significant amounts of superoxide or H2O2. It is likely that the reversible inhibition of microtubule assembly and function caused by glutathione oxidants requires only increased glutathione disulfide and is not dependent on subsequent accumulation of other metabolites.