Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema
Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema
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DOI：
10.1183/09031936.00174612
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发表时间：
2014-01-01
影响因子：
24.3
通讯作者：
Sandford, Andrew J.
中科院分区：
文献类型：
--
作者：
Ishii, Takeo;Abboud, Raja T.;Sandford, Andrew J.
肺泡巨噬细胞通过产生基质金属蛋白酶（MMPs）、组织蛋白酶及其抑制剂、组织金属蛋白酶抑制剂和胱抑素C在慢性阻塞性肺疾病中发挥重要作用。我们假设这些分子的表达水平由肺泡巨噬细胞在基线和刺激后将受到基因型的影响，并与慢性阻塞性肺疾病表型相关，定量PCR和ELISA/明胶酶谱法分别用于调查mRNA和蛋白质的表达水平。结果表明，MMP 12 mRNA基础表达水平与肺一氧化碳弥散量/肺泡容积、1 s用力呼气量/用力肺活量呈负相关。脂多糖刺激的MMP 12蛋白表达水平与肺一氧化碳弥散量/肺泡容积呈负相关，与肺气肿程度呈正相关。MMP 1 mRNA基础表达与肺气肿程度呈正相关。组织蛋白酶L蛋白水平与用力呼气容积（1 s %）预测值呈正相关，提示MMP 12和MMP 1表达增加可能在肺气肿的发病机制中起一定作用。组织蛋白酶L和MMP 9可能参与了气流受限的发生。
Alveolar macrophages play an important role in chronic obstructive pulmonary disease via production of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases and cystatin C. We hypothesised that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with chronic obstructive pulmonary disease phenotypes.Quantitative PCR and ELISAs/gelatine zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed.The results showed that basal expression level of MMP12 mRNA was inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and to forced expiratory volume in 1 s/forced vital capacity after correction for multiple comparisons. The expression level of MMP12 protein stimulated with lipopolysaccharide was also inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and was positively related to the extent of emphysema. The basal expression of MMP1 mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with forced expiratory volume in 1 s % predicted.We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation.