Evidence for cyclic GMP and calcium mediation of lymphocyte activation by mitogens
Coffey, R.G.; Hadden, E.M.; Hadden, J.W.
Journal of Immunology 119(4): 1387-1394
1977
ISSN/ISBN: 0022-1767 PMID: 197170 Document Number: 119706
The results of 47 experiments indicate that the lectin mitogens, PHA . After preexposure to Con A in the absence of Ca, the addition of Ca produces increases in cGMP. Mitogen-induced increases in lymphocyte cGMP are probably totally Ca2+-dependent, yet only in part dependent on extra-cellular Ca2+. The interpretation is confirmed with a divalent cation ionophore A23187, which induced lymphocyte proliferation in close association with Ca2+-dependent increases in cGMP; at higher concentrations it inhibits the mitogenic effects in association with Mg2+-dependent increases in cAMP. Dose-response curves for each agent showed that this capacity to increase cGMP levels was correlated with the optimal mitogenic concentration as determined by assay of DNA synthesis. cGMP probably participates in the positive aspects of mitogen action and cAMP probably participates in the inhibitory aspects. Coparticipation of cGMP and Ca2+ as essential mediators of the mitogenic signal is a sound hypothesis.