The effect of colchicine and vinblastine on the chemotactic response of human monocytes.

We examined the effects of colchicine or vinblastine in the chemotactic response of human peripheral blood mononuclear leukocytes. The number of monocytes migrating into 5-µm micropore filters in response to an activated serum stimulus was significantly decreased in the presence of colchicine or vinblastine concentrations ≥10−6 M. Colchicine, but not vinblastine, at 10−7 M or 10−8 M actually enhanced chemotactic migration. There was a qualitatively similar effect of both drugs on monocyte unstimulated migration. The ultrastructural effects of colchicine or vinblastine on monocytes under conditions of chemotaxis were evaluated by allowing the monocytes to migrate to the surface of an 0.45-µm micropore filter. In the absence of tubulin-binding drugs, the untreated monocytes responded to the chemotactic gradient by flattening on the filter surface, and portions of the pseudopod entered the filter pores. The nucleus was in the middle of the cell, and the centriole with the associated radial array of microtubules tended to be located beneath the nucleus. In contrast, colchicine or vinblastine treatment at ≥10−6 M resulted in fewer cells adherent to the filter surface. Cells were rounded, with centripetal localization of granules and mitochondria. There was an increased tendency for the nucleus to be located at the periphery of the cell. In many cells, the pseudopod was narrower and actually extended deeper within the filter pores than seen in untreated cells. In a few treated cells, the pseudopod contained unusually large amounts of microfilaments, and the plasma membrane was extensively undulated, yet the pseudopod did not enter the filter pores. Colchicine or vinblastine at ≥10−6 M greatly decreased counts of centriole-associated microtubules. Colchicine, but not vinblastine, at 10−9 M to 10−7 M slightly enhanced microtubule assembly. The data support a role for microtubules in maintaining normal intracellular organelle distribution and cell shape. Although pseudopod formation and migration toward a chemotactic stimulus can occur in the absence of microtubules, intact microtubules appear to modulate these cellular functions in a way that results in the most efficient migratory response.