In vivo and in vitro effects of colchicine and vinblastine on the secretory process of antibody-producing cells.

The sensitivity of the secretory process of antibody-synthesizing cells to microtubule-binding drugs, colchicine and vinblastine sulfate, was studied. Rats were immunized by footpad injections of horseradish peroxidase, and the popliteal lymph nodes were removed at various times after injection. Both in vivo effects of colchicine and in vitro effects of colchicine and vinblastine were studied. Quantitative data were obtained with in vitro drug-treated cells by labeling with L-3H-leucine and by measuring the secreted and the cytoplasmic immunoglobulins. It was found that inhibition of immunoglobulin secretion was about 78% and 93% by colchicine and vinblastine, respectively. the results obtained with the latter drug were more difficult to interpret because it also inhibited the biosynthesis of total proteins, and particularly that of immunoglobulins. Immunocytochemical studies of the in vivo and in vitro drug-treated cells performed by light and electron microscopy showed that in antibody-containing cells the Golgi area was often occupied by dilated antibody-containing vesicles, probably derived from the Golgi apparatus. In a few of these cells it was observed that antibody-containing rough endoplasmic reticulum was markedly dilated. the above results demonstrate that both microtubule-binding agents, colchicine and vinblastine, are potent inhibitors of the secretory process of plasma cells and seem to indicate that a correlation may exist between ultrastructural changes and inhibition of secretion.