A cytoskeleton-dependent pathway for induction of IL-2 production and a cytoskeleton-independent pathway for IL-2-mediated signal transduction.
We have used the synthetic microtubule inhibitor Tubulozole C in order to study the role of the microtubule system in human lymphocyte activation. Microtubule disruption prior to activation with phytohemagglutinin (PHA) resulted in a drastic reduction of IL-2 production. Similarly, using OKT3 or PHA as stimulators, a substantial decrease in proliferation was observed. Although IL-2 receptor analysis performed on the stimulated and antitubular-treated lymphocytes showed a 2-fold decrease in high-affinity and a 100-fold decrease in low-affinity IL-2 receptor expression, a proliferative response to externally added rIL-2 was noticed. This occurred provided the triggering agent was excluded or added in suboptimal concentrations. These results indicate that intact microtubules are necessary for PHA/OKT3-induced proliferation and IL-2 production, but not for IL-2-induced proliferation.
Nihlmark
E L
EL
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
Lindqvist
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D003599:Cytoskeleton / Q000502:physiology*; D004148:Dioxolanes / Q000494:pharmacology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D004148:Dioxolanes; D007378:Interleukins; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; C040422:tubulazole