Chlamydia pneumoniae dissemination and atherosclerosis

肺炎衣原体传播和动脉粥样硬化

• 批准号: 15590399
• 负责人: YAMAGUCHI Hiroyuki
• 金额: $ 2.3万
• 依托单位: Osaka University (2004)Kyorin University (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590399/
• 关键词: Chlamydia pneumoniae; PBMC; dissemination; Real-time RT-PCR; Atherosclerosis; NOD mice; Animal model; real-time RT-PCR法; ルイスラット; 末梢血液; 生体内伝播; クラミジア・ニューモニエ; 未梢血液PBMC; real-time PCR; Syber green; 動物モデル; 生菌; RNA

Current studies have revealed that the obligate intracellular bacterium Chlamydia (Chlamydophila) pneumoniae is associated not only with respiratory diseases but also with atherosclerosis. In the present study, to understand the viability and growth potential of C.pneumoniae detected in blood of healthy persons, we first attempted to detect C.pneumoniae transcript in peripheral blood mononuclear cells (PBMCs) obtained from 70 healthy donors by real-time RT-PCR method. The presence of C.pneumoniae transcript in PBMCs from blood of healthy human donors was assessed by real-time RT-PCR-using primers for C.pneumoniae 16S rRNA. Out of 70 donors (18.5 %) showed the presence of bacterial transcript in cultured PBMCs. Prevalence of bacterial detection and bacterial numbers were significantly increased in PBMNC cultures incubated with cycloheximide. These results showed that viable C.pneumoniae might be present in healthy human PBMCs. Although several studies reported C.pneumoniae systemic diss … More emination from lung in animal model by DNA-based qualitative methods, the lack of a suitable animal model for permitting viable C.pneumonia dissemination from lung to blood has impeded the understanding of how viable C.pneumoniae can reach blood vessels and trigger the development of atherosclerosis. Therefore, we next studied the susceptibility of non-obese diabetic (NOD) mice to dissemination of viable C.pneumoniae from lung to blood, as detected by real-time RT-PCR. Following multiple intranasal inoculations, bacteria in lung were detected in NOD mice with diabetes (38.5%, n=13) as well as ICR mice (40%, n=10), but prevalence of bacteria in NOD mice without diabetes [Pre-diabetic NOD mice (n=8) and non-diabetic retired NOD mice (n=13)] was very low (5.2%, n=21). The bacteria were only detected in cultured PBMCs (53.8 %) of the NOD mice with diabetes. The prevalence of bacterial detection appeared to be increased in PBMC cultures incubated with hydrocortisone. Cultivation of C.pneumoniae from cultured PBMCs from all NOD mice was unsuccessful. Results of immunostaining with fluorescein isothiocyanate-conjugated anti-Chlamydia monoclonal antibody also showed the presence of bacterial antigens in the lungs and the PBMCs judged as positive by the RT-PCR. Thus, diabetic NOD mouse is sensitive to C.pneumoniae infection in which a possible dissemination of viable bacteria from lung to blood, and the animal model established in this study may be useful for understanding dissemination of C.pneumoniae infection. Less

目前的研究表明，胸部细胞内细菌（衣原体）肺炎不仅与呼吸道疾病有关，而且与动脉粥样硬化有关。在本研究中，为了了解健康人血液中检测到的pneumoniae的生存能力和生长潜力，我们首先试图检测到外周血液单核细胞（PBMC）中的脑脑转录本，通过实时RT-PCR方法从70个健康供体获得的。通过实时的RT-PCR使用底漆来评估C. pneumoniae 16S rRNA的实时RT-PCR引物，评估了健康捐助者血液中PBMC中的C. pneumoniae转录本。在70名捐助者中（18.5％），在培养的PBMC中表明了细菌转录本。在与环己酰亚胺孵育的PBMNC培养物中，细菌检测和细菌数量的患病率显着增加。这些结果表明，健康的人类PBMC可能存在可行的c.pneumoniae。尽管有几项研究报道了基于DNA的定性方法在动物模型中肺部肺炎全身性疾病的c. pneumoniae c. permination，但缺乏适合可行的动物模型来允许可行的动物模型从肺到血液中的pneumoniae传播，这阻碍了人们对可行的c.pneumoniae的理解能够到达血管并触发了Atheclosis的发育。因此，我们接下来研究了非肥胖糖尿病（NOD）小鼠的敏感性，该小鼠对可行的C. pneumoniae从肺部传播到血液，如实时RT-PCR所检测到的那样。在多次鼻内接种后，在糖尿病（38.5％，n = 13）和ICR小鼠（40％，n = 10）的NOD小鼠中检测到肺中的细菌，但是在没有糖尿病的NOD小鼠中细菌的患病率是糖尿病患者的患病率[前糖尿病小鼠（N = 8）和非糖尿病的N = 21. N = 21 13 = 21）。仅在患有糖尿病的NOD小鼠的培养的PBMC（53.8％）中检测到细菌。在与氢化可的松孵育的PBMC培养物中，细菌检测的患病率似乎增加了。来自所有NOD小鼠培养的PBMC的c.pneumoniae均未成功。荧光素异硫氰酸酯偶联的抗神经毒素单克隆抗体的免疫染色的结果也表明，肺中存在细菌抗原，而PBMC被RT-PCR判断为阳性。这就是糖尿病点头小鼠对脑乳杆菌感染敏感，其中可能从肺部传播可行的细菌，而这项研究中建立的动物模型可能有助于理解脑杆菌感染的传播。较少的

项目成果

Yamaguchi H. et al.: "Chlamydia pneumoniae resists antibiotics in lymphocytes."Antimicrobial Agents and Chemotherapy. 47(6). 1972-1975 (2003)

Yamaguchi H.等人：“肺炎衣原体对淋巴细胞中的抗生素具有抵抗力。”抗菌药物和化疗。

Prevalence of viable Chlamydia pneumoniae in peripheral blood mononuclear cells of healthy blood donors.

健康献血者外周血单核细胞中活肺炎衣原体的患病率。

• 发表时间: 2004
• 期刊: Transfusion 44
• 作者: Takahashi M;Taguchi H;Yamaguchi H;Osaki T;Komatsu A;Kamiya S.;Hiroyuki Yamaguchi et al.
• 通讯作者: Hiroyuki Yamaguchi et al.

Matsnaga K et al.: "Legionella pneumophila suppresses macrophage interleukin-12 production by activating the p42/44 mitogen-activated preotein kinase cascade."Infection and Immunity. 71(11). 6672-6675 (2003)

Matsnaga K 等人：“嗜肺军团菌通过激活 p42/44 丝裂原激活的蛋白激酶级联来抑制巨噬细胞白细胞介素 12 的产生。”感染和免疫。

Yamaguchi H. et al.: "Prevalence of viable Chlamydia pneumoniae in PBMNCs of Healthy donors."Transfusion. in press. (2004)

Yamaguchi H. 等人：“健康捐献者的 PBMNC 中存活的肺炎衣原体的患病率。”输血。

Chlamydia pneumoniae resists antibiotics in lymphocytes.

肺炎衣原体对淋巴细胞中的抗生素具有抵抗力。

• 发表时间: 2003
• 期刊: Antimicrobial Agents and Chemotherapy 47
• 作者: Takahashi M;Taguchi H;Yamaguchi H;Osaki T;Komatsu A;Kamiya S.;Hiroyuki Yamaguchi et al.;Motomichi Takahashi et al.;Yamaguchi H. et al.;Yamaguchi H. et al.
• 通讯作者: Yamaguchi H. et al.