Alpha-1-antitrypsin (AAT) anomalies are associated with lung disease due to rapidly growing mycobacteria and AAT inhibits Mycobacterium abscessus infection of macrophages
Alpha-1-antitrypsin (AAT) anomalies are associated with lung disease due to rapidly growing mycobacteria and AAT inhibits Mycobacterium abscessus infection of macrophages
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DOI：
10.1080/00365540701225744
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Shapiro, Leland
中科院分区：
文献类型：
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作者：
Chan, Edward D.;Kaminska, Aleksandra M.;Shapiro, Leland
快速生长的分枝杆菌（RGM）在环境中普遍存在，但仅在一小部分暴露个体中引起肺部疾病。这种对疾病的可变易感性意味着由于宿主防御的弱点而容易受到RGM感染。由于大多数感染RGM肺病的人没有已知的宿主防御缺陷，因此可能存在易患RGM感染的未表征的宿主缺陷。α-1-抗胰蛋白酶（AAT）是一种宿主因子，可以保护个体免受呼吸道感染。因此，我们评估AAT蛋白异常作为RGM肺病的危险因素。在100例RGM肺病患者的队列中，分枝杆菌（M.）寄生虫是最常见的微生物，在64例（64%）受试者中分离。异常AAT蛋白存在于27%的队列中，这是美国人群中异常AAT蛋白估计患病率的1.6倍（p = 0.008）。在体外研究中，AAT和丝氨酸蛋白酶的合成抑制剂抑制M。单核细胞衍生的巨噬细胞的巨噬细胞感染高达65%（p
Rapidly growing mycobacteria (RGM) are ubiquitous in the environment but cause lung disease in only a fraction of exposed individuals. This variable susceptibility to disease implies vulnerability to RGM infection due to weakness in host defense. Since most persons who contract RGM lung disease have no known host defense defect, it is likely that uncharacterized host deficiencies exist that predispose to RGM infection. Alpha-1-antitrypsin (AAT) is a host factor that may protect individuals from respiratory infections. Therefore, we assessed AAT protein anomalies as a risk factor for RGM lung disease. In a cohort of 100 patients with RGM lung disease, Mycobacterium (M.) abscessus was the most prevalent organism, isolated in 64 (64%) subjects. Anomalous AAT proteins were present in 27% of the cohort, which is 1.6 times the estimated prevalence of anomalous AAT proteins in the United States population (p = 0.008). In in vitro studies, both AAT and a synthetic inhibitor of serine proteases suppressed M. abscessus infection of monocyte-derived macrophages by up to 65% (p