Jutel M, Blaser K, Akdis C A
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
J Investig Allergol Clin Immunol. 2005;15(1):1-8.
In addition to its well-characterized effects in the acute inflammatory and allergic responses, histamine has been shown to affect chronic inflammation and regulate several essential events in the immune response. Histamine can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization, and effector functions leading to chronic inflammation. On the other hand histamine acting through its receptor (HR) type 2 positively interferes with the peripheral antigen tolerance induced by T regulatory (Treg) cells in several pathways. Histamine also regulates antigen-specific TH1 and TH2 cells, as well as related antibody isotype responses. These findings provide suitable explanation for the observations in the experimental model of asthma showing that allergic inflammatory responses and bronchial hyperresponsiveness may be susceptible to HR1 blockade. Apparently, the various effects of histamine on immune regulation are due to differential expression and regulation of 4 histamine receptors and their distinct intracellular signals. In addition, differences in affinities of these receptors is highly decisive on the biological effects of histamine and drugs that target histamine receptors. This article highlights novel discoveries in histamine immunobiology and discusses their relevance to the allergic inflammatory responses.
除了在急性炎症和过敏反应中具有明确的作用外,组胺还被证明会影响慢性炎症并调节免疫反应中的几个关键事件。组胺可以选择性地将主要效应细胞募集到组织部位,并影响它们的成熟、激活、极化和效应功能,从而导致慢性炎症。另一方面,组胺通过其2型受体(HR)在多条途径中对由调节性T(Treg)细胞诱导的外周抗原耐受性产生正向干扰。组胺还调节抗原特异性TH1和TH2细胞以及相关抗体的同种型反应。这些发现为哮喘实验模型中的观察结果提供了恰当的解释,表明过敏性炎症反应和支气管高反应性可能对HR1阻断敏感。显然,组胺对免疫调节的各种作用归因于4种组胺受体的差异表达和调节及其独特的细胞内信号。此外,这些受体亲和力的差异对组胺和靶向组胺受体的药物的生物学效应具有高度决定性。本文重点介绍了组胺免疫生物学的新发现,并讨论了它们与过敏性炎症反应的相关性。