Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation
Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation
复制标题
DOI：
10.4049/jimmunol.175.4.2589
复制
发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Cataldo, DD
中科院分区：
文献类型：
--
作者：
Gueders, MM;Balbin, M;Cataldo, DD
基质金属蛋白酶（MMPs）参与炎症反应，包括哮喘相关的气道炎症。MMP-8主要由中性粒细胞产生，最近有报道在哮喘患者的支气管肺泡灌洗液（BALF）中增加。为了评价MMP-8在哮喘中的作用，我们检测了OVA致敏的哮喘小鼠模型肺组织中MMP-8的表达，并探讨了MMP-8缺失对变应原诱导的支气管炎症的影响。暴露于过敏原的C57 BL/6小鼠的肺中MMP-8的产生增加。过敏原暴露后，MMP-8-1-小鼠发生气道炎症，其特征在于BALF中嗜酸性粒细胞炎症增加以及气道壁中嗜酸性粒细胞和嗜酸性粒细胞浸润增加。MMP-8缺乏与BALF和血清中IL-4和抗OVA IgE和IgG 1水平的升高相关。虽然过敏原暴露诱导增强LPS诱导的CXC趋化因子，KC，和MIP-2的水平在BALF和肺实质中，没有观察到两种基因型之间的差异。MMP-8（-/-）小鼠肺中炎性细胞凋亡减少。我们的研究第一次证明了MMP-8在控制过敏原诱导的肺部炎症过程中嗜酸性粒细胞和嗜酸性粒细胞浸润中的重要作用，并证明MMP-8的抗炎作用部分是由于调节炎性细胞凋亡。
Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has recently been reported to be increased in the bronchoalveolar lavage fluid (BALF) from asthmatic patients. To evaluate the role of MMP-8 in asthma, we measured MMP-8 expression in lung tissue in an OVAsensitized mouse model of asthma and addressed the effect of MMP-8 deletion on allergen-induced bronchial inflammation. MMP-8 production was increased in lungs from C57BL/6 mice exposed to allergens. After allergen exposure, MMP-8-1-mice developed an airway inflammation characterized by an increased neutrophilic inflammation in BALF and an increased neutrophilic and eosinophilic infiltration in the airway walls. MMP-8 deficiency was associated with increased levels of IL-4 and antiOVA IgE and IgG1 in BALF and serum, respectively. Although allergen exposure induced an enhancement of LPS-induced CXC chemokine, KC, and MIP-2 levels in BALF and lung parenchyma, no difference was observed between the two genotypes. Inflammatory cell apoptosis was reduced in the lungs from MMP-8(-/-) mice. For the first time, our study evidences an important role of MMP-8 in the control of neutrophilic and eosinophilic infiltration during allergen-induced lung inflammation, and demonstrates that the anti-inflammatory effect of MMP-8 is partly due to a regulation of inflammatory cell apoptosis.