Histamine H4 and H2 receptors control histamine-induced interleukin-16 release from human CD8+ T cells
Histamine H4 and H2 receptors control histamine-induced interleukin-16 release from human CD8+ T cells
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DOI：
10.1124/jpet.102.036939
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发表时间：
2002-10-01
影响因子：
3.5
通讯作者：
Bacon, KB
中科院分区：
文献类型：
--
作者：
Gantner, F;Sakai, K;Bacon, KB
已知组胺会触发人类 CD8(+) 细胞释放白细胞介素 (IL)-16。然而，目前已知的组胺受体亚型 (H-1-H-4) 在这种炎症反应中的各自作用尚未得到充分表征。组胺刺激从外周血中纯化的人CD8(+)T淋巴细胞导致IL-16的基础释放在24小时内增加5至8倍，并且这种增加分别被H-2选择性拮抗剂西咪替丁或H-3和H-4受体拮抗剂硫哌丁胺显着阻断。 H-1 拮抗剂吡拉明的作用有限。对 H-2 (dimaprit)、H-3/4 (R-(-)-α-甲基组胺) 和 H4 (clobenpropit) 具有选择性的激动剂能够诱导生物活性 IL-16 的释放，因为 CD8(+) 细胞上清液诱导 CD4(+) 细胞迁移，而抗 IL-16 抗体可消除这种迁移。此外，淋巴细胞与百日咳毒素预孵育消除了由 G(i/o) 偶联 H-4 受体激活而非 H-2 受体激活引发的 IL-16 释放。信使RNA表达研究证实H-4、H-2和H-1在人CD8(+)淋巴细胞中表达，而H-3 mRNA完全不存在。研究的所有白细胞群均表达 H-4 mRNA，其中在嗜酸性粒细胞、树突状细胞和扁桃体 B 细胞中表达水平最高。在人肺、气管和各种人肺来源的细胞，如成纤维细胞、支气管平滑肌细胞、上皮细胞和内皮细胞中也检测到H-4表达。由于其中许多是已知的 IL-16 来源，免疫细胞和肺细胞表达的 H-4 受体可能在控制哮喘等炎症性疾病的介质中发挥一般作用。
Histamine is known to trigger the release of interleukin (IL)-16 from human CD8(+) cells. However, the individual roles of the presently known histamine receptor subtypes (H-1-H-4) in this inflammatory response have not been fully characterized. Histamine stimulation of human CD8(+) T lymphocytes purified from peripheral blood led to a 5- to 8-fold increase in the basal release of IL-16 within 24 h, and this increase was significantly blocked by the H-2-selective antagonist, cimetidine, or by thioperamide, an antagonist of H-3 and H-4 receptors, respectively. The H-1 antagonist pyrilamine showed limited effects. Agonists selective for H-2 (dimaprit), H-3/4 (R-(-)-alpha-methylhistamine), and H4 (clobenpropit) were capable of inducing the release of bioactive IL-16 because CD8(+) cell supernatants induced CD4(+) cell migration, which was abrogated by an anti-IL-16 antibody. Furthermore, preincubation of lymphocytes with pertussis toxin abolished IL-16 release triggered by activation of the G(i/o) coupled H-4 receptor but not by the H-2 receptor. Messenger RNA expression studies confirmed H-4, H-2, and H-1 expression in human CD8(+) lymphocytes, whereas H-3 mRNA was completely absent. All leukocyte populations investigated expressed mRNA for H-4, with highest levels found in eosinophils, dendritic cells, and tonsil B cells. H-4 expression was also detected in human lung, trachea, and various cells of human lung origin, such as fibroblasts, bronchial smooth muscle cells, epithelial, and endothelial cells. Since many of those are known sources of IL-16, immune cell- and lung cell- expressed H-4 receptors may have a general role in the control of this mediator of inflammatory disorders such as asthma.