A Study on the Role of Protease Produced by Vibrio cholerae non-01 in the Pathogenic Mechanism of Sepsis.

霍乱弧菌non-01产生的蛋白酶在脓毒症致病机制中作用的研究。

• 批准号: 10670262
• 负责人: ICHINOSE Yoshio
• 金额: $ 1.73万
• 依托单位: Institute of Tropical Medicine, Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670262/
• 关键词: Vibrio cholerae non-01; metalloprotease; invasive mechanism; Vibrio cholerae; invasive factor

There are many reports on the cases of Vibrio cholerae infection which may extend to extra-intestinal organs. It can result in sepsis and multiple organ failure especially in immunocompromised hosts. It is then considered that a metalloprotease produced by Vibrio cholerae may be involved in its invasive mechanisms of vibrios into tissues or vessels. Because it is a permeability factor to activate kinin cascade and an activating factor of a matrix metalloprotease produced by leukocytes migrating in the inflammatory lesion. We were then trying to develop an animal model of sepsis due to Vibrio cholerae 019 to elucidate the invasive mechanisms of Vibrio cholerae. The results obtained through the study on the role of metalloprotease in pathogenic mechanisms of Vibrio cholerae and histopathological findings in sepsis model are as follows ;(1)Improvement of purification method of choleraprotease.(2)Establishment of assay system of choleraprotease using immunoblotting with ECL kit.(3)Analysis of nicking site of cholera toxin by choleraprotease.(4)Development of mouse sepsis model using Vibrio cholerae 019.(5)Involvement of choleraprotease in the pathogenic mechanism of sepsis.(6)Involvement of iNOS in the pathogenic mechanism of sepsis.

有关霍乱弧菌感染可能蔓延至肠外器官的病例报道较多。它可能导致败血症和多器官衰竭，尤其是在免疫功能低下的宿主中。据认为，霍乱弧菌产生的金属蛋白酶可能参与其弧菌侵入组织或血管的机制。因为它是激活激肽级联的通透性因子，也是炎症病灶内白细胞迁移产生的基质金属蛋白酶的激活因子。然后我们试图建立霍乱弧菌019引起的败血症动物模型，以阐明霍乱弧菌的侵袭机制。通过金属蛋白酶在霍乱弧菌致病机制中的作用及脓毒症模型的组织病理学研究结果如下：（1）霍乱蛋白酶纯化方法的改进。（2）ECL免疫印迹霍乱蛋白酶测定体系的建立试剂盒。(3)霍乱蛋白酶分析霍乱毒素的切口位点。(4)霍乱毒素的开发霍乱弧菌019小鼠脓毒症模型。(5)霍乱蛋白酶参与脓毒症发病机制。(6)iNOS参与脓毒症发病机制。

项目成果

Y.Ichinose, H.Kwase, R.Kato, S.Imamura, T.Handa & T.Tsuji.: "Hemaaglutinin/protease of Vibrio cholerae with diminished ability to cleave cholera toxin being a minor virulent factor for human diarrhea."Jpn.J.Infect.Dis.. 52. 44 (1999)

Y.Ichinose、H.Kwase、R.Kato、S.Imamura、T.Handa

M.Ehara,M.Iwomi.Y.Ichinose: "Induction of fimbriated Vibrio cholesoe 0139"Clin.Drog.Lobo.Immun.. 5. 65-69 (1998)

M.Ehara，M.Iwomi.Y.Ichinose：“流苏弧菌 cholesoe 0139 的诱导”Clin.Drog.Lobo.Immun.. 5. 65-69 (1998)

T.Tsuji, Y.Asano, T.Handa, Y.Honma, Y.Ichinose and T.Yokochi.: "Induction of apoptosis in lymphoid tissues of mice after intra-muscular injection of enterotoxigenic. Escherichia coli enterotoxin"Immunobiology.. 201. 377-390 (1999)

T.Tsuji、Y.Asano、T.Handa、Y.Honma、Y.Ichinose 和 T.Yokochi.：“肌内注射产肠毒素的小鼠淋巴组织中诱导细胞凋亡。大肠杆菌肠毒素”免疫生物学.. 201

M.Ehora: "Development of Hyperfimbriuter strains of Vibrio choclerae 01"Microbiology and Immunology. 44(6). 439-446 (2000)

M.Ehora：“霍氏弧菌 01 的 Hyperfimbriuter 菌株的开发”微生物学和免疫学。

一瀬休生: "疾患別最新処方感染症・寄生虫3.チフスパラチフス,6.細菌食中毒"メジカルビュー社. 4 (1998)

Kyusei Ichinose：“按疾病划分的传染病和寄生虫的最新处方 3. 伤寒和副伤寒，6. 细菌性食物中毒” Medical View Inc. 4 (1998)