Koarai Akira, Ichinose Masakazu, Ishigaki-Suzuki Satsuki, Yamagata Shunsuke, Sugiura Hisatoshi, Sakurai Eiko, Makabe-Kobayashi Yoko, Kuramasu Atsuo, Watanabe Takehiko, Shirato Kunio, Hattori Toshio, Ohtsu Hiroshi
Division of Respiratory and Infectious Diseases and Department of Cellular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Am J Respir Crit Care Med. 2003 Mar 1;167(5):758-63. doi: 10.1164/rccm.200206-619OC. Epub 2002 Dec 12.
Histamine has a variety of airway actions and is considered to be an important mediator in asthma. This study examined the role of endogenous histamine in allergic airway eosinophil recruitment and hyperresponsiveness using L-histidine decarboxylase gene knockout mice. Histamine levels of the airways in L-histidine decarboxylase knockout mice were largely diminished compared with wild-type mice. Inhalation challenge with ovalbumin (OVA) in OVA-sensitized wild-type mice caused eosinophil accumulation in the lung as well as airway hyperresponsiveness to methacholine 3 days after the challenge. The eosinophil recruitment was significantly reduced in the knockout mice. In the bone marrow, the proliferation of eosinophils was enhanced after OVA challenge in the wild-type mice; however, the proliferation was significantly reduced in the knockout mice. The induction of P-selectin in the lung after OVA challenge was also inhibited in the knockout mice. In contrast, airway hyperresponsiveness was not suppressed in the knockout mice. These results suggest that endogenous histamine is involved in the accumulation of eosinophils into the airways after allergic challenge, possibly acting in the bone marrow and producing P-selectin in the airways. Furthermore, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model.
组胺具有多种气道作用，被认为是哮喘中的一种重要介质。本研究使用L-组氨酸脱羧酶基因敲除小鼠，研究内源性组胺在过敏性气道嗜酸性粒细胞募集和高反应性中的作用。与野生型小鼠相比，L-组氨酸脱羧酶敲除小鼠气道中的组胺水平大幅降低。在卵清蛋白（OVA）致敏的野生型小鼠中，吸入OVA激发后3天，肺部出现嗜酸性粒细胞积聚以及气道对乙酰甲胆碱的高反应性。敲除小鼠中的嗜酸性粒细胞募集显著减少。在骨髓中，野生型小鼠经OVA激发后嗜酸性粒细胞的增殖增强；然而，敲除小鼠中的增殖显著减少。敲除小鼠中OVA激发后肺中P-选择素的诱导也受到抑制。相比之下，敲除小鼠中的气道高反应性未被抑制。这些结果表明，内源性组胺参与过敏性激发后嗜酸性粒细胞在气道中的积聚，可能作用于骨髓并在气道中产生P-选择素。此外，在我们目前的模型中，变应原诱导的气道高反应性似乎独立于气道嗜酸性粒细胞增多而发生。
