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

我们利用我们建立的组氨酸脱羧酶基因敲除小鼠，评估了组胺在体内情况下的作用。该基因在肥大细胞、嗜碱性粒细胞、嗜碱性粒细胞、胃细胞等产生组胺的细胞中表达。我们阐明了组胺在各种变态反应性疾病、睡眠状态和胃液分泌中的活性。我们还重新阐明了组胺与感染和慢性肉芽肿的关系。例如，在全身过敏反应中，组胺对控制体温和呼吸起着重要作用，但不影响血压。基因敲除的小鼠在清醒时表现出典型的睡眠波的脑电。野生型小鼠胃液分泌受胃泌素诱导，而基因敲除小鼠胃液分泌不明显。组胺的存在阻碍了腹膜炎的恢复。组胺在皮下植入棉线引发的慢性肉芽肿形成中起重要作用。除了这些体内表型外，我们还使用骨髓来源的肥大细胞观察到了耐人寻味的证据。一旦在含有组胺的培养液中培养肥大细胞，这些组胺就被吸收到分泌颗粒中，并在LgE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.