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The Inhibition of Initial Steps of Lymphocyte Transformation by Cytochalasin B¹

From the Institut für Immunologie der Universität, Heidelberg, and Max-Planck-Institut für Immunobiologie, Freiburg, Germany, and Department of Immunology, Research Institute, The Hospital for Sick Children, Toronto, Canada

Abstract

CB was shown to inhibit the PHA-induced activation of rabbit lymph node lymphocytes as assessed by the incorporation of ³H-uridine into RNA or ³H-thymidine into DNA. This suppression was dose dependent with an optimum of 10 µg CB/ml (20. 8 µM). Mitogen-activated lymphocytes escaped the inhibitory effect of the drug when CB was added later than 1 hr after the addition of PHA. CB also suppressed the activation of membrane phospholipid metabolism which occurs among the earliest detectable changes in activated lymphocytes. Thus the incorporation of ¹⁴C-choline, ¹⁴C-acetate, or ¹⁴C-oleate into lecithin in the presence of PHA and CB was the same as the level of their incorporation in unstimulated lymphocytes. The increased incorporaion of ¹⁴C-oleate into lecithin of the plasma membrane of activated lymphocytes was similarly prevented in the presence of CB. In contrast, CB exhibited no or only a marginal effect on the phospholipid turnover of unstimulated lymphocytes. Our results point to plasma membrane phospholipid metabolism as the possible site of CB interference with the lymphocyte activation.

Footnotes

¹ Supported by Grants (Fe 130/2 and Re 281/2) from the Deutsche Forschungsgemeinschaft and (MA-4875) from the Medical Research Council of Canada.

² Send correspondence to: Dr. Klaus Resch, Institut für Immunologie der Universität, Im Neuenheimer Feld 305, D-6900 Heidelberg, Germany.

³ Max-Planck-Institute für Immunbiologie.

⁴ Research Institute, The Hospital for Sick Children.