Mechanism of action of colchicine. II. Effects of colchicine and its analogs on phagocytosis and chemotaxis

CH.xd;, iI-HAN: Mechmanisnm of actiolm of colcimicimme. II. Effects of colchicine and its aimalogs omm pimagocytosis amm(l chmemotaxis in vitro. J. Pimarmacol. Exp. Ther. 194: 159-164, 1975. Coicimicimme, desacety!metimylcolchmicilme a ndl colcimiceine suppress the pimagocytosis of sta rclm grammules by rabbit peritoneal pohymorpimonuchear leukocytes in vitro. Trimethylcolchi-cinic acid and! 2-d!esnmethmyhcoichmicine ghmcoside imave no effect on )imagocytosis. Colchmicine, at concentrations as higim as 1 X 10 M, imas no effect on chemotaxis of polymorpimo-nuclear leukocvtes in response to inmmune complex-acti’ated cimemotactic factors or on the motility of timese cells. These results do not support the contention that time slip-pression of phmagocytosis or chemotaxis l)laYS a significant role in time anti-inflammatory activity of coichmicine. In time preceding report, evidence was pre-sented! in support of time imypothesis that the antimitotic ammd time anti-inflammatory effects of coichicine simare a comnmoim mechanism, i.e., time disruption of time microtubules in cells (Mala-vista, 1968). It is not clear which cells are af-fected directly by coicimicine in its anti-inflam-matory actions, but polvmorpimonuclear leukocytes (PMN) are one likely target. The dissolution of microtubules may affect the func-tion of PMX in a number of ways. Since mi-crotui)ules a re intimately associated functionally withm structure mmd locomotion of cells, the dis-ruptiomm of time organdies could bring about a suppressiomm of P\IN phagocytosis, chemotaxis, motility, lysosomal vacuolization (formation of I)!magoh’s050me5) and degrammulation (extra ccliii-lar release of granular eimzymes)-pimenomena known to coimtrihute to time inflammatory re-Receiveth for publication Augumst 9, 1974. Send reprint requests to: Yi-Han Chang, Phm.D.