Cyclosporin A inhibits mitogen-activated but not phorbol ester-activated locomotion of human lymphocytes.
Human blood lymphocytes acquire locomotor capacity during 24 hr culture with mitogens such as monoclonal anti-CD3 antibodies, phytohaemagglutinin (PHA), or Staphylococcus aureus Cowan strain (SAC). Activation of locomotor capacity by these agents is blocked by the presence of cyclosporin A (greater than or equal to 10 ng per ml), as measured by inhibition of the development of morphological polarization of the cells in culture and inhibition of their capacity to invade collagen gels. The response to OKT3 is inhibited by lower doses of cyclosporin than the responses to SAC or PHA. Phorbol myristate acetate (PMA) induces locomotion of lymphocytes in culture that is not inhibited by cyclosporin. Cyclosporin has no effect on the locomotion of lymphocytes that already possess locomotor capacity. Thus it neither inhibits immediate stimulus-induced polarization of lymphocytes direct from blood, nor reverses polarization of lymphocytes that have acquired motility in culture. These results suggest that cyclosporin prevents events, occurring during the G1 phase of growth, that are necessary for non-motile lymphocytes to acquire locomotor capacity, but has no effect on the locomotor mechanism itself in already motile cells.
D000911:Antibodies, Monoclonal / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005782:Gels; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology*; D008934:Mitogens / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D005782:Gels; D008934:Mitogens; D003094:Collagen; D013755:Tetradecanoylphorbol Acetate