Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma
Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma
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DOI：
10.1152/ajplung.00042.2009
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发表时间：
2010-02-01
影响因子：
4.9
通讯作者：
D'Armiento, Jeanine
中科院分区：
文献类型：
--
作者：
Mehra, Divya;Sternberg, David I.;D'Armiento, Jeanine
Mehra D，斯滕贝格DI，Jia Y，坎菲尔德S，Lemaitre V，Nkyimbeng T，怀尔德J，Sonett J，D 'Armiento J.哮喘小鼠模型中表达人MMP-9的转基因小鼠中淋巴细胞运输改变和气道反应性降低。美国生理学杂志肺细胞分子生理学298：L189-L196，2010年。首次发表于2009年11月25日; doi：10.1152/ajplung.00042.2009.-基质金属蛋白酶-9（MMP-9）被认为促进哮喘气道白细胞外渗和细胞外重塑。仔细的描述性研究表明，MMP-9水平较高的哮喘患者的痰中，然而，MMP-9活性增加的后果尚未确定在这种疾病。我们在小鼠肺组织巨噬细胞中表达人MMP-9的转基因小鼠中诱导哮喘，以确定人MMP-9表达对气道炎症的直接影响。用卵清蛋白免疫转基因（TG）和野生型（WT）小鼠并攻击。卵白蛋白激发后48小时，测定气道高反应性（AHR），并评价支气管肺泡灌洗液（BALF）和肺组织中的炎性细胞浸润。TG组和WT组小鼠的基线炎症水平相似，通过致敏和卵清蛋白激发，两组均建立了肺嗜酸性粒细胞增多症。与WT对照组相比，致敏和激发转基因组中的AHR显著降低。尽管两组的BALF细胞总数相似，但TG组灌洗液中的淋巴细胞数量与WT组相比显著减少（0.25 +/- 0.08 vs. 0.89 +/- 0.53; P = 0.0032）。此外，发现TG动物的引流淋巴细胞比WT小鼠更大。在两组中观察到相同数量的巨噬细胞、嗜酸性粒细胞和中性粒细胞。与WT小鼠相比，发现致敏TG中的IL-13水平较低。这些结果表明，人MMP-9和AHR之间的反比关系，并表明MMP-9的表达改变了白细胞外渗，减少淋巴细胞在哮喘气道壁的积累。
Mehra D, Sternberg DI, Jia Y, Canfield S, Lemaitre V, Nkyimbeng T, Wilder J, Sonett J, D'Armiento J. Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma. Am J Physiol Lung Cell Mol Physiol 298: L189-L196, 2010. First published November 25, 2009; doi: 10.1152/ajplung.00042.2009.-Matrix metalloproteinase-9 (MMP-9) is hypothesized to facilitate leukocyte extravasation and extracellular remodeling in asthmatic airways. Careful descriptive studies have shown that MMP-9 levels are higher in the sputum of asthmatics; however, the consequence of increased MMP-9 activity has not been determined in this disease. We induced asthma in transgenic mice that express human MMP-9 in the murine lung tissue macrophage to determine the direct effect of human MMP-9 expression on airway inflammation. Transgenic (TG) and wild-type (WT) mice were immunized and challenged with ovalbumin. Forty-eight hours after the ovalbumin challenge, airway hyperresponsiveness (AHR) was measured, and inflammatory cell infiltration was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue. Baseline levels of inflammation were similar in the TG and WT groups of mice, and pulmonary eosinophilia was established in both groups by sensitization and challenge with ovalbumin. There was a significant reduction in AHR in sensitized and challenged trangenics compared with WT controls. Although total BALF cell counts were similar in both groups, the lymphocyte number in the lavage of the TG group was significantly diminished compared with the WT group (0.25 +/- 0.08 vs. 0.89 +/- 0.53; P = 0.0032). In addition, the draining lymphocytes were found to be larger in the TG animals compared with the WT mice. Equal numbers of macrophages, eosinophils, and neutrophils were seen in both groups. IL-13 levels were found to be lower in the sensitized TG compared with the WT mice. These results demonstrate an inverse relationship between human MMP-9 and AHR and suggest that MMP-9 expression alters leukocyte extravasation by reducing lymphocyte accumulation in the walls of asthmatic airways.