Interleukin-2 stimulus-response coupling is calcium independent.
This study investigated the role of calcium (Ca2+) as a second messenger in the stimulus-response coupling of interleukin 2 (IL 2) binding to its specific receptor that results in lymphocyte proliferation. Although the Ca2+ channel blockers verapamil, nifedipine, and diltiazem induced a dose-dependent inhibition of [3H]-thymidine incorporation by HT-2 cells in response to recombinant human and purified rat IL 2, the stimulation indices of the treated and untreated cells were equivalent. Stimulation of HT-2 cells with recombinant human IL 2 (rIL 2) did not result in an increase in the concentration of intracellular free Ca2+ [( Ca2+]i), using the fluorescent intracellular Ca2+ indicator Fura-2AM. Conversely, partially purified rat IL 2 did cause an increase in [Ca2+]i that was not inhibited by the channel blockers or by chelation of extracellular free Ca2+. Thus, contaminating components in the partially purified rat IL 2, and not the IL 2 itself, resulted in increased [Ca2+]i by mobilization from intracellular stores. These results demonstrate that inhibition of lymphocyte proliferation by verapamil, nifedipine, and diltiazem is not due to an uncoupling of the IL 2 lymphokinetic signal, and stimulation of HT-2 cells using rIL 2 does not increase [Ca2+]i, and thus does not employ Ca2+ as a second messenger.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D004110:Diltiazem / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium