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

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。

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.