Accelerated clearance of Escherichia coli in experimental peritonitis of histamine-deficient mice
Accelerated clearance of Escherichia coli in experimental peritonitis of histamine-deficient mice
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DOI：
10.4049/jimmunol.169.4.1978
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发表时间：
2002-08-15
影响因子：
4.4
通讯作者：
Ohtsu, H
中科院分区：
文献类型：
--
作者：
Hori, Y;Nihei, Y;Ohtsu, H
我们制备了一个实验性腹膜炎的模型，通过引入大肠杆菌到组胺缺乏小鼠的腹腔中，通过破坏组氨酸脱羧酶（HDC）的基因，独特的组胺合成酶。接种E.大肠杆菌注入HDC-/-（组胺缺乏）小鼠的腹腔，他们消除了大肠杆菌。大肠杆菌的效率比野生型小鼠更高。E.大肠杆菌接种在HDC+/+小鼠中，尽管在HDC-/-小鼠的腹膜细胞中仅检测到痕量。两种组胺激动剂（6-[2-（4-咪唑基）乙氨基]-N-（4-三氟甲基苯基）庚烷甲酰胺（H-1）和二甲双胍（H-2））均损害E. HDC-/-小鼠腹腔中的大肠杆菌，表明H1和H2受体的激活抑制了清除。相反，两种H-1和H-2受体拮抗剂西咪替丁和吡拉明可促进E.大肠杆菌中的HDC+/+小鼠。HDC-/-小鼠的吞噬作用似乎增强，因为HDC-/-小鼠腹腔中的中性粒细胞数量显著增加。在存在组胺激动剂6-[2-（4-咪唑基）乙氨基]-N-（4-三氟甲基苯基）庚烷甲酰胺和二甲双胍的情况下，中性粒细胞募集的增强受到抑制。在这篇报道中，组胺首次被证明是大肠杆菌中的一种重要介质。大肠杆菌感染性腹膜炎模型，造成细菌消除延迟。这也增加了使用抗组胺药治疗细菌感染的可能性。
We prepared a model of experimental peritonitis by introducing Escherichia coli into the peritoneal cavity of the histamine-deficient mice generated by a disruption of the gene for histidine decarboxylase (HDC), the unique histamine-synthesizing enzyme. When we inoculated E. coli into the peritoneal cavities of the HDC-/- (histamine-deficient) mice, they eliminated E. coli more efficiently than did the wild-type mice. Histamine was released efficiently from the peritoneal cells after E. coli inoculation in HDC+/+ mice, although only trace amounts were detected in the peritoneal cells of HDC-/- mice. Two histamine agonists (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)hepatanecarboxamide (H-1) and dimaprit (H-2)) impaired the clearance of E. coli from the peritoneal cavity in HDC-/- mice, suggesting that the activation of both H, and H, receptors suppresses the clearance. In contrast, two kinds of H-1 and H-2 receptor antagonists, cimetidine and pyrilamine, promoted the clearance of E. coli in HDC+/+ mice. Phagocytosis appeared to be enhanced in HDC-/- mice, since the number of neutrophils in the peritoneal cavity of HDC-/- mice was markedly increased. This enhanced recruitment of neutrophils was suppressed in the presence of the histamine agonists, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)hepatanecarboxamide and dimaprit. In this report histamine was first shown to be an important mediator in an E. coli infectious peritonitis model, causing a delay in the elimination of bacteria. This also raised the possibility of the use of antihistamine drugs for bacterial infection.