抄録
The culture of mouse spleen cells with concanavalin A (Con A) or phytohemagglutinin (PHA) increased histidine decarboxylase (HDC) activity as a function of incubation time. The histamine level of the medium increased in parallel with the increase in HDC activity. Lymphocyte proliferation induced by Con A was enhanced by cimetidine, a histamine H2-antagonist, in the absence of exogenous histamine. Dimaprit, an H2-agonist, blocked lymphocyte blastogenesis at high doses (>10-5M). Diphenhydramine, an H1-antagonist, abolished mitogenesis induced by Con A. At low doses (10-9-10-7 M), the H1-agonist 2-pyridylethylamine augumented mitogenesis mediated by Con A. The addition of alphafluoromethylhistidine or histaminase (EC 1.4.3.6), at low doses, to the culture enhanced Con-A-dependent lymphocyte proliferation. At high doses they inhibited the reaction. Histamine itself augmented [3H]thymidine uptake by lymphocytes induced by Con A at the low doses of10-13-10-11 M;at higher doses (>10-5 M), it suppressed this response. These results suggest that mitogen-induced lymphocyte proliferation is regulated by histamine, formed in the system per se through the action of HDC.