Furukawa Fukumi, Yoshimasu Takashi, Yamamoto Yuki, Kanazawa Nobuo, Tachibana Takao
Department of Dermatology, Wakayama Medical University, Wakayama City, Japan.
Autoimmun Rev. 2009 May;8(6):495-9. doi: 10.1016/j.autrev.2008.12.016. Epub 2009 Jan 20.
It is likely that mast cell and histamine metabolism are involved in autoimmune tissue injury such as cutaneous lupus erythematosus (LE) because different histamine receptors can regulate Th1 and Th2 cells. In order to verify the role of the axis of mast cell-histamine metabolism-histamine receptor, the autoimmune mouse has been investigated. The MRL/Mp-lpr/lpr (MRL/lpr) mouse is a good model for the spontaneous development of skin lesions similar to those seen in human LE. In skin lesions from MRL/l mice, there are many infiltrating T cells and mast cells in the dermis and impaired histamine metabolism, in which the low activity of histamine-N-methyltransferase and the related prolonged effects of histamine in the skin tissue seem to play a definite pathological role in the development of spontaneous lupus-like eruptions. The expression of H2R on the mast cell decreases within these skin lesions at 5 months of age. It is interesting that the activity of HMT runs in parallel with the expression of H2R over the time course of the skin changes in MRL/l mice, but the relationship between these two observations remains obscure. The accumulation of mast cells expressing H2R and prolonged effects of histamine may occur to regulate the production of Th1 and Th2 cytokines in the skin lesions of MRL/l mice.
肥大细胞和组胺代谢可能参与了自身免疫性组织损伤,如皮肤红斑狼疮(LE),因为不同的组胺受体可以调节Th1和Th2细胞。为了验证肥大细胞-组胺代谢-组胺受体轴的作用,对自身免疫小鼠进行了研究。MRL/Mp-lpr/lpr(MRL/lpr)小鼠是一种很好的模型,可自发出现类似于人类LE所见的皮肤病变。在MRL/l小鼠的皮肤病变中,真皮中有许多浸润的T细胞和肥大细胞,组胺代谢受损,其中组胺-N-甲基转移酶活性低以及组胺在皮肤组织中的相关延长作用似乎在自发性狼疮样皮疹的发展中起明确的病理作用。在5月龄时,这些皮肤病变中肥大细胞上H2R的表达降低。有趣的是,在MRL/l小鼠皮肤变化的时间过程中,HMT的活性与H2R的表达平行,但这两个观察结果之间的关系仍不清楚。表达H2R的肥大细胞的积累和组胺的延长作用可能会调节MRL/l小鼠皮肤病变中Th1和Th2细胞因子的产生。