The fibrinolytic system in dissemination and matrix protein deposition during a mycobacterium infection.

The fibrinolytic system in dissemination and matrix protein deposition during a mycobacterium infection.
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DOI:
10.1016/s0002-9440(10)63680-2
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发表时间:
2003-08
期刊:
The American journal of pathology
影响因子:
--
通讯作者:
J. Sato;J. Schorey;V. Ploplis;E. Haalboom;Liana Krahule;F. Castellino
J. Sato;J. Schorey;V. Ploplis;E. Haalboom;Liana Krahule;F. Castellino
中科院分区:
其他
文献类型:
--
作者:
J. Sato;J. Schorey;V. Ploplis;E. Haalboom;Liana Krahule;F. Castellino

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已知纤溶系统在细菌感染的炎症反应中起重要作用。在本研究中,纤溶系统的蛋白质组分和鸟分枝杆菌的感染性之间的关系进行了分析。感染是通过非侵入性肠道内施用M. avium 724在单独缺乏纤溶酶原、组织型纤溶酶原激活物、尿激酶型纤溶酶原激活物和尿激酶型纤溶酶原激活物受体的小鼠中的表达,沿着野生型对照小鼠。在整个10周的感染中,所有小鼠基因型之间的肺集落计数没有差异。然而,在组织型纤溶酶原激活物和纤溶酶原缺陷小鼠中,M.对其他器官的影响。然而,M.在整个10周的感染期间,不同小鼠种群之间肝、脾和肺中的禽类生长率没有差异。感染后5周和10周的组织化学和免疫组化分析表明,纤溶酶原缺陷小鼠,与野生型小鼠相比,增强了纤维蛋白和纤连蛋白沉积,以及增加中性粒细胞浸润的肝脏肉芽肿。这些结果表明,纤溶酶(原)在肉芽肿细胞外基质蛋白的周转中起作用,并在M.从肺中取出的禽流感病毒因此,纤溶酶(原)的功能是限制慢性分枝杆菌感染期间肉芽肿中进行性纤维化。
The fibrinolytic system is known to play an important role in the inflammatory response to bacterial infections. In the present study, relationships between protein components of the fibrinolytic system and infectivity by Mycobacterium avium were analyzed. Infections were initiated through noninvasive intratracheal administration of M. avium 724 in mice individually deficient for plasminogen, tissue-type plasminogen activator, urokinase-type plasminogen activator, and urokinase-type plasminogen activator receptor, along with wild-type control mice. There were no differences in lung colony counts among all mouse genotypes throughout a 10-week infection. However, in tissue-type plasminogen activator and plasminogen-deficient mice an earlier dissemination of M. avium to other organs was observed. Nevertheless, the M. avium growth rates in the liver, spleen, and lung did not differ between the various mouse populations throughout a 10-week infection. Histochemical and immunohistochemical analyses at 5 and 10 weeks after infection demonstrated that plasminogen-deficient mice, compared to wild-type mice, had enhanced fibrin and fibronectin deposition, as well as increased neutrophil infiltration within liver granulomas. These results suggest that plasmin(ogen) plays a role in the turnover of extracellular matrix proteins within granulomas and has a limited effect in the early dissemination of M. avium from lungs. Thus, plasmin(ogen) functions in limiting progressive fibrosis in the granuloma during a chronic mycobacterial infection.