Histamine: its novel role as an endogenous regulator of Con A-dependent T cell proliferation.
OBJECTIVE
The roles of histamine formed by the macrophage - T lymphocyte system were evaluated in the regulation of lymphocyte proliferation using mice lacking histamine receptors.


METHODS
Mice deficient in histamine type 1 (H1R), type 2 (H2R) or both receptors were employed to estimate possible intervention of the receptors in the histamine-dependent lymphocyte proliferation.


RESULTS
Histamine was produced de novo by spleen cells. Con A-dependent T cell proliferation decreased when histamine produced in the culture was degraded by the addition of histaminase. The H2R-deficient mice also showed a significant decrease in the Con A-dependent T cell proliferation, whereas it was not modulated in the H1R-deleted mice. Consistent with the reduction in T cell proliferation, there was a significant down-regulation of the production of IL-2, a T cell growth factor, in the H2R-deficient mice. Con A-dependent IL-2 synthesis was abrogated by the addition of histaminase.


CONCLUSIONS
Con A-dependent T cell proliferation is (up)regulated by histamine produced de novo through the H2R, suggesting that histamine is a newly found regulator of T cell proliferation.
Nakane
H
H
Department of Animal Cell Function, Bioscience and Biotechnology Center, Nagoya University, 464-8601, Chikusa, Nagoya, Japan.
Sonobe
Y
Y
Watanabe
T
T
Nakano
K
K
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D003208:Concanavalin A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D006632:Histamine / Q000378:metabolism / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*; D015854:Up-Regulation
D007376:Interleukin-2; D003208:Concanavalin A; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing)