Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation
Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation
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DOI：
10.1189/jlb.0910486
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发表时间：
2011-02-01
影响因子：
5.5
通讯作者：
Pedotti, Rosetta
中科院分区：
文献类型：
--
作者：
Lapilla, Marilena;Gallo, Barbara;Pedotti, Rosetta
组胺可能参与了MS及其动物模型EAE的病理过程。我们探讨了组胺和特异性HR激动剂对髓鞘自身反应性T细胞活化和迁移能力的影响。我们表明，组胺在体外抑制增殖和IFN-γ的产生的小鼠T细胞活化PLP 139 -151。这些作用被H1 R激动剂HTMT和H2 R激动剂dimaelide模仿，并且与ERK 1/2激酶的活化减少和细胞周期抑制剂p27 Kip-1的水平增加相关，两者都参与T细胞增殖和无能。H1 R和H2 R激动剂减少自发和趋化因子诱导的自身反应性T细胞粘附ICAM-1在体外和阻断这些细胞在发炎的脑微循环在体内牢固的粘附。因此，组胺通过H1 R和H2 R抑制髓鞘自身反应性T细胞的活化及其通过发炎的BBB的能力。旨在干扰组胺轴的策略可能与CNS自身免疫性疾病的治疗相关。J.利瓦克89：259-267; 2011.
Histamine may contribute to the pathology of MS and its animal model EAE. We explored the effects of histamine and specific HR agonists on activation and migratory capacity of myelin-autoreactive T cells. We show that histamine in vitro inhibits proliferation and IFN-gamma production of mouse T cells activated against PLP139-151. These effects were mimicked by the H1R agonist HTMT and the H2R agonist dimaprit and were associated with reduced activation of ERK1/2 kinase and with increased levels of cell cycle inhibitor p27Kip-1, both involved in T cell proliferation and anergy. H1R and H2R agonists reduced spontaneous and chemokine-induced adhesion of autoreactive T cells to ICAM-1 in vitro and blocked firm adhesion of these cells in inflamed brain microcirculation in vivo. Thus histamine, through H1R and H2R, inhibits activation of myelin-autoreactive T cells and their ability to traffic through the inflamed BBB. Strategies aimed at interfering with the histamine axis might have relevance in the therapy of autoimmune disease of the CNS. J. Leukoc. Biol. 89: 259-267; 2011.