Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency
Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency
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DOI：
10.1038/ni773
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发表时间：
2002-04-01
影响因子：
30.5
通讯作者：
Kheradmand, F
中科院分区：
文献类型：
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作者：
Corry, DB;Rishi, K;Kheradmand, F
清除募集的免疫细胞是解决炎症反应所必需的。我们发现基质金属蛋白酶2（MMP 2）作为白细胞介素13（IL-13）依赖性调节环的一部分，通过促进炎性细胞进入气道腔来抑制炎症。MMP 2（-/-）小鼠表现出稳健的哮喘表型，并增加了对过敏原诱导的窒息的易感性。然而，尽管MMP 2的缺乏减少了细胞流入支气管肺泡灌洗液（BAL），但许多炎性细胞在肺实质中积累。MMP 2（-/-）小鼠的BAL缺乏正常的趋化活性，而来自相同小鼠的肺炎性细胞显示适当的趋化反应。因此，MMP 2建立了肺炎性细胞流出和防止致死性窒息所需的趋化梯度。
Clearance of recruited immune cells is necessary to resolve inflammatory reactions. We show here that matrix metalloproteinase 2 (MMP2), as part of an interleukin 13 (IL-13)-dependent regulatory loop, dampens inflammation by promoting the egress of inflammatory cells into the airway lumen. MMP2(-/-) mice showed a robust asthma phenotype and increased susceptibility to asphyxiation induced by allergens. However, whereas the lack of MMP2 reduced the influx of cells into bronchoalveolar lavage (BAL), numerous inflammatory cells accumulated in the lung parenchyma. BAL of MMP2(-/-) mice lacked normal chemotactic activity, whereas lung inflammatory cells from the same mice showed appropriate chemotactic responses. Thus, MMP2 establishes the chemotactic gradient required for egression of lung inflammatory cells and prevention of lethal asphyxiation.