Effects of cytochalasins on lymphocytes: mechanism of inhibition of rosette formation.

The mechanisms operative in the inhibition by cytochalasins of human peripheral blood T lymphocytic rosette formation with sheep erythrocytes remain obscure in the light of the multiplicity of biologic effects of cytochalasins. Moreover, we have shown the existence of three distinct classes of cytochalasin-binding sites (H-, M-, and L-sites) in such lymphocytes (J. Biol. Chem. 256:1290-1300, 1981). We have, therefore, explored the mechanism of rosette inhibition and present evidence that shows: a) Inhibition of rosetting is not caused by inhibition of glucose transport in lymphocytes; b) cytochalasin binding to the H- and M-sites, both integral plasma membrane proteins, is not involved in the effect; c) nonspecific partitioning of cytochalasins in the plasma membrane lipids of lymphocytes appears unlikely to explain the effect; d) evidence presented in this paper strongly suggests that cytochalasin binding to the actin associated L-site mediates the inhibition of rosetting. We conclude that cytoskeletal microfilaments play a critical role in the normal functioning of cell surface receptors for binding to sheep erythrocytes.