Vinblastine: Colchicine-like Effects on Human Blood Leukocytes During Phagocytosis

Vinblastine and colchicine interfere with the normal organization of microtubules both in the mitotic spindle of dividing cells—causing metaphase arrest—and in the cytoplasm of nondividing cells such as polymorphonuclear leukocytes, with effects less well understood. In addition to this ultrastructural alteration, colchicine has other morphologic, enzymic, and metabolic effects on phagocytizing leukocytes, that may contribute to its anti-inflammatory properties in vivo. In the present work, effects of vinblastine were compared to those of colchicine. The effects of vinblastine 2.5 x 10^-5 M were in all respects similar to those of colchicine and, on a molar basis, at least as strong. There was inhibition of the increased oxygen consumption and glucose-1-¹⁴C oxidation that normally accompany phagocytosis. There was also inhibition of lysosomal degranulation and the formation of digestive vacuoles, indicated both in morphologic studies and in measurements of granule-associated acid phosphatase activity after phagocytosis. In this system there was no demonstrable effect either on the ingestion process itself or on the intracellular killing of Staphylococcus aureus. If, however, leukocytes in buffer were incubated with preopsonized staphylococci, they ingested bacteria more rapidly than in the serum system. Under those circumstances, if the concentration of drug was doubled (to 5 x 10^-5 M), there was still no difference in ingestion of bacteria between drug-treated and control leukocytes, but both vinblastine and colchicine inhibited intracellular killing of staphylococci. However, this inhibition, though statistically significant, was trivial compared to the percentages of the inocula ingested and killed by both treated and control leukocytes. These findings support the hypothesis that common structural and functional effects of vinblastine and colchicine may ultimately be traced to common ultrastructural effects on microtubules. Moreover, microtubules may facilitate the fusion of lysosomes with vacuoles containing ingested material.