Assessment of function of histamine using histidine decarboxylase gene-manupulated mice

使用组氨酸脱羧酶基因操作的小鼠评估组胺的功能

• 批准号: 13470018
• 负责人: OHTSU Hiroshi
• 金额: $ 9.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470018/
• 关键词: histamine; knockout mice; histidine decarboxylase; transgenic mice; gene; infection; allergy; behavior; 肥満細胞; 胃酸分泌; 概日リズム; H2受容体; SAGE法

We estimated the role of histamine in the in vivo situation using histidine decarboxylase gene knockout mice generated by us. This gene is expressed in the cells able to produce histamine, which are mast cell, basophil, neron, gastric cell, etc. We clarified the activity of histamine in various allergic diseases, sleep state and secretion of gastric juice. We also newly clarified the relation of histamine to infection and chronic granuloma. For example, in the systemic anaphylaxis reaction, histamine plays a important role for the control of body temperature and respiration, but it does not affect the blood pressure. The knockout mice show electroencepharogram typical for the sleeping wave during waking time. The secretion of gastric juice was induced by gastrin in the wild type mice however it was seased in the knockout mice.The existence of histamine retard the recovery from peritonitis produced by intraperitoneal injection of E..coli. Histamine is important for the chronic granuloma formation triggered with subcutaneous cotton thread implantation. In addition to these in vivo phenotypes we observed intriguing evidence using bone marrow-derived mast cells. Onece we cultured the mast cell in the medium containing histamine, these histamine were absorbed into the secretory granules and could be secreted after the stimulation with lgE and anti-IgE.

我们估计的作用，组胺在体内的情况下，使用组氨酸脱羧酶基因敲除小鼠由我们产生。该基因在肥大细胞、嗜碱性粒细胞、神经元、胃细胞等能产生组胺的细胞中表达，阐明了组胺在各种过敏性疾病、睡眠状态和胃液分泌中的活性。我们还新阐明了组胺与感染和慢性肉芽肿的关系。例如，在全身性过敏反应中，组胺对体温和呼吸的控制起重要作用，但不影响血压。敲除小鼠在清醒时显示出典型的睡眠波脑电图。在野生型小鼠中，胃泌素可诱导胃液分泌，而在基因敲除小鼠中，则可抑制胃液分泌，组胺的存在可延缓腹腔注射E.杆菌组胺在皮下埋线引发的慢性肉芽肿形成中起重要作用。除了这些在体内表型，我们观察到有趣的证据，使用骨髓来源的肥大细胞。将肥大细胞置于含组胺的培养基中培养，这些组胺被吸收到分泌颗粒中，并在IgE和抗IgE刺激下分泌。

项目成果

Yoko Kobayashi-Makabe: "The control effect of histamine on the body temperature and respiratory function in systemic anaphylaxis"J. Allergy Clin. Immunol. 110. 298-303 (2002)

Yoko Kobayashi-Makabe：“组胺对全身过敏反应中体温和呼吸功能的控制作用”J。

Akira Koarai: "Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness"Am J Respir Crit Care Med. 167. 758-763 (2003)

Akira Koarai：“L-组氨酸脱羧酶的破坏可减少气道嗜酸性粒细胞增多，但不会减少高反应性”Am J Respir Crit Care Med。

Noriyasu Hirasawa: "Enhancement of neutrophil infiltration in histidine decarboxylase-deficient mice"Immunol. 107. 217-221 (2002)

Noriyasu Hirasawa：“组氨酸脱羧酶缺陷小鼠中中性粒细胞浸润的增强”免疫。

Tanaka, S: "Gastric acid secretion in L-histidine decarboxylase deficient mice"Gastroenterology. 122. 145-155 (2002)

Tanaka, S：“L-组氨酸脱羧酶缺陷小鼠的胃酸分泌”胃肠病学。

Yasuhiko Kubota, Chihiro Ito, Eiichi Sakurai, Eiko Sakurai, Takehiko Watanabe and Hiroshi Ohtsu: "Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice"J. Neurochem.. 83. 837-845 (2002)

Yasuhiko Kubota、Chihiro Ito、Eiichi Sakurai、Eiko Sakurai、Takehiko Watanabe 和 Hiroshi Ohtsu：“组胺缺乏小鼠中甲基苯丙胺诱导的运动活性和行为敏感性增加”J.