Effects of cytoskeletal disrupting agents on replication of bovine endothelium

Abstract

Colchicine and vinblastine inhibited endothelial cell migration but had no effect on the stimulation of replication seen at wound edges in cultures of endothelium at stationary density. This is in contrast to the effects of cytochalasins which inhibit both migration and replication at wound edges. Moreover, colchicine and vinblastine stimulated cell replication in the unwounded, confluent monolayer. This effect has kinetics similar to the stimulation of replication at a wound edge and is associated with an initial retraction of cell borders, leaving gaps between cells. Cytochalasin D inhibited the growth response to microtubule disrupting agents but did not prevent cell retraction. Stimulation of replication by microtubule disrupting agents was not dependent on serum but was synergistic with serum in cultures rinsed repeatedly with serum-free medium. The replication occurred prior to any cell loss. When, however, cells were allowed to complete mitosis, about one-half of the daughter cells detached from the monolayer so that there was no increase in cell density. We conclude that microtubule disrupting agents are the first agents found to be effective in stimulating growth of vascular endothelium at saturation density. These data further suggest that colchicine and vinblastine stimulate cell growth in a manner similar to wounding, where cell movement is a prerequisite to cell replication.