Drugs which disrupt microtubules do not inhibit the initiation of lymphocyte activation

Abstract

LYMPHOCYTES are activated to grow and divide when mitogens such as plant lectins bind to surface receptors. Several hypotheses have been advanced to explain how a signal which results from the interaction of an activating ligand with its receptors, may be transduced across the membrane to initiate cell activation¹. Recently Edelman and co-workers proposed a model in which a complex, composed of receptor, microfilaments and microtubules serves as a regulator for lymphocyte mitogenesis^2–6. From experiments in which colchicine, when added to stimulated cultures at various time intervals, gradually lost its capacity to suppress subsequent DNA synthesis over 30–40 h, it was concluded that drugs which disrupt microtubules block lymphocyte activation at the point at which a lymphocyte becomes committed to undergoing growth and division^5,6. However, other similar experiments^7,8 showed that colchicine was effective in suppressing DNA synthesis up to 48 h after the addition of mitogen. If indeed the microtubules are involved in the initiation of lymphocyte activation, then the disruption of these cytoplasmic structures should also affect cellular events which occur before DNA synthesis⁹.