Ohtsu Hiroshi, Kuramasu Atsuo, Tanaka Satoshi, Terui Tadashi, Hirasawa Noriyasu, Hara Masahiro, Makabe-Kobayashi Yoko, Yamada Noboru, Yanai Kazuhiko, Sakurai Eiko, Okada Mikiko, Ohuchi Kazuo, Ichikawa Atsushi, Nagy Andras, Watanabe Takehiko
Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Eur J Immunol. 2002 Jun;32(6):1698-708. doi: 10.1002/1521-4141(200206)32:6<1698::AID-IMMU1698>3.0.CO;2-7.
Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.
组氨酸脱羧酶（HDC）在哺乳动物体内由组氨酸合成内源性组胺。为评估组胺在皮肤过敏反应中的作用，我们使用了缺乏组胺的HDC基因敲除小鼠。在被动皮肤过敏反应（PCA）试验后，未在HDC-/-小鼠中观察到血浆外渗反应。化合物48/80是一种肥大细胞颗粒耗竭剂，在HDC+/+小鼠中可引起血浆外渗，但在HDC-/-小鼠中未引起外渗。有趣的是，口服给予的组胺在HDC-/-小鼠的皮肤中分布，并且在这些补充组胺的小鼠中，在注射化合物48/80和进行PCA试验后观察到血浆外渗反应。HDC-/-小鼠培养的骨髓来源肥大细胞从补充组胺的培养基中摄取组胺并进入分泌颗粒。吸收的组胺会响应与PCA试验中相同的抗原和抗体组合而释放。与速发型反应不同，在三硝基氯苯激发（致敏后）后观察到的迟发型超敏反应表现为耳部皮肤增厚，在HDC+/+和HDC-/-小鼠之间未显示出差异。因此，在过敏性皮肤反应中，组胺被证明是一种重要的介质，特别是在速发型过敏模型中对血浆外渗而言。
