engleski

Effects of SMS 201-995 on blastic proliferation of lymphocytes induced by different transmembrane pathways

In previous reports we demonstrated that SOM and its long acting analogue SMS 201-995 have in vivo the immunosuppressive and antiproliferative properties. Their effects in vitro were, however, dependent also on type of activation of lymphocytes. To characterise better these events we investigated the effects of SMS on blastic transformation of human peripheral blood mononuclear cells stimulated by: 1) anti CD3 monoclonal antibody, 2) phorbol myristate acetat (PMA) and 3) by anti CD3+PMA. To obtain an insight into temporal susceptibility of activated lymphocytes SMS was applied in the culture 15 minutes before, simultaneously with, or 1 and 12h after the initiation of blastogenesis. Additionally the longitudinal FACS analysis of surface markers on cells stimulated with CD3+PMA and treated by SMS (from 0-14h) was done. The data have shown that SMS does not block anti CD3-induced proliferation, but inhibits the proliferation induced by PMA and anti-CD3+PMA in all tested intervals. This antiproliferative effect of SMS, however, was not preceded by any significant change in percentage of CD4+, CD8+, IL-2R+ T cells on activated cells. In contrast to these finding SMS induced greater expression of IL-2R on spontaneously proliferating CD4+ and CD8+ cells. The data emphasise that antiproliferative effects of SMS on human lymphocytes depend on type of stimulation and suggest that SMS may have different effects on resting and activated lymphocytes.

SMS 201-995; blastogenesis induced by anti CD3 mAb and/or PMA; phenotype of activated lymphocytes

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