Interferon gamma induction of pulmonary emphysema in the adult murine lung.

Interferon gamma induction of pulmonary emphysema in the adult murine lung.
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成年鼠肺中肺肺气肿的干扰素γ诱导。

DOI:
10.1084/jem.192.11.1587
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发表时间:
2000-12-04
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Elias JA
Elias JA
中科院分区:
其他
文献类型:
--
作者:
Wang Z;Zheng T;Zhu Z;Homer RJ;Riese RJ;Chapman HA Jr;Shapiro SD;Elias JA

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慢性阻塞性肺疾病患者的肺中同时存在含有CD 8+淋巴细胞、中性粒细胞和巨噬细胞的慢性炎症和肺气肿。虽然这种炎症反应被认为是导致这些组织中可见的重塑,但炎症导致肺气肿的机制尚未确定。在这里,我们证明,干扰素γ(IFN-γ),一个突出的产品的CD 8+细胞,导致肺气肿与肺泡扩大,增加肺容量,增强肺顺应性,和巨噬细胞和嗜中性粒细胞丰富的炎症时,诱导靶向,在一个转基因的方式,以成年小鼠肺。在这些小鼠中还观察到显著的蛋白酶和抗蛋白酶改变。包括基质金属蛋白酶(MMP)-12和组织蛋白酶B、H、D、S和L的诱导和激活,MMP-9的加工,以及分泌性白细胞蛋白酶抑制剂的选择性抑制。当IFN-γ在肺组织中表达时,其引起肺气肿和肺蛋白酶/抗蛋白酶平衡的改变。
Chronic inflammation containing CD8+ lymphocytes, neutrophils, and macrophages, and pulmonary emphysema coexist in lungs from patients with chronic obstructive pulmonary disease. Although this inflammatory response is believed to cause the remodeling that is seen in these tissues, the mechanism(s) by which inflammation causes emphysema have not been defined. Here we demonstrate that interferon γ (IFN-γ), a prominent product of CD8+ cells, causes emphysema with alveolar enlargement, enhanced lung volumes, enhanced pulmonary compliance, and macrophage- and neutrophil-rich inflammation when inducibly targeted, in a transgenic fashion, to the adult murine lung. Prominent protease and antiprotease alterations were also noted in these mice. They included the induction and activation of matrix metalloproteinase (MMP)-12 and cathepsins B, H, D, S, and L, the elaboration of MMP-9, and the selective inhibition of secretory leukocyte proteinase inhibitor. IFN-γ causes emphysema and alterations in pulmonary protease/antiprotease balance when expressed in pulmonary tissues.
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发表时间: 1999-11-01
影响因子: 24.7
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发表时间: 1996-11-12
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