A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection
A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection
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DOI：
10.1016/j.tube.2004.07.001
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发表时间：
2004-01-01
期刊：
影响因子：
3.2
通讯作者：
Majka, S
中科院分区：
文献类型：
--
作者：
Izzo, AA;Izzo, LS;Majka, S
目的：宿主对肺部结核分枝杆菌 (Mtb) 感染的反应导致肉芽肿形成，以限制感染，但宿主免疫细胞也提供了 Mtb 持续存在的环境。肉芽肿的形成需要免疫细胞浸润和同时肺组织的广泛重塑，我们假设这是基质金属蛋白酶 (MMP) 活性增加的结果。设计：通过气管内接种感染强毒 Mtb (H37Rv) 的 C57BL/6 小鼠用 MMP 活性合成抑制剂 (BB-94) 治疗。在感染后 90 天的时间里，对小鼠进行集落形成单位、肉芽肿形态、白细胞募集和细胞因子水平进行评估。结果：与媒介物处理的 Mtb 感染小鼠相比，BB-94 处理的小鼠在疾病早期肺部和血源性 Mtb 数量显着减少，早期肉芽肿内胶原蛋白沉积增加，肺部白细胞募集显着减少。细胞因子表达在各组之间没有显着差异。结论：早期肉芽肿形成的事件可以通过抑制 MMP 活性、减少白细胞募集（感染期间 MMP 的主要来源）、促进肉芽肿的形成和减少 Mtb 的血液传播来改变。 (C) 2004 Elsevier Ltd. 保留所有权利。
Objective: The host response to pulmonary Mycobacterium tuberculosis (Mtb) infection results in granuloma formation in an effort to limit infection, but the host immune cells also provide an environment in which Mtb persists. Granuloma formation requires immune cell infiltration and concurrent extensive remodeling of pulmonary tissue which we hypothesize to be the result of increased matrix metalloproteinases (MMP) activity.Design: C57BL/6 mice infected with virulent Mtb (H37Rv) via intratracheal inoculation were treated with a synthetic inhibitor of MMP activity (BB-94). Mice were assessed for colony forming units, granuloma morphology, leukocyte recruitment and cytokine levels over 90 days of infection.Results: BB-94 treated mice had significantly decreased numbers of pulmonary and blood-borne Mtb early during disease, increased collagen deposition within early granulomas and significantly decreased pulmonary leukocyte recruitment when compared to vehicle-treated, Mtb-infected mice. Cytokine expression did not differ significantly between groups.Conclusion: Events of early granuloma formation can be modified by inhibiting MMP activity, by decreasing leukocyte recruitment, a major source of MMPs during infection, enhancing the establishment of granulomas and decreasing blood-borne dissemination of Mtb. (C) 2004 Elsevier Ltd. All rights reserved.