Aldonyte R, Jansson L, Ljungberg O, Larsson S, Janciauskiene S
Department of Pathology, University Hospital Malmo, Malmö, Sweden.
Histopathology. 2004 Dec;45(6):587-92. doi: 10.1111/j.1365-2559.2004.02021.x.
The damage to lung tissue in chronic obstructive pulmonary disease (COPD) may involve the progressive loss of pulmonary vascular endothelial cells. Endothelial binding of alpha1-antitrypsin (alpha1-AT) derived from plasma has been identified, and alpha1-AT deficiency is a known genetic risk factor associated with alpha1-AT polymerization and COPD development. Therefore, in the present study we aimed to investigate if alpha1-AT is present on the lung vascular endothelium, and if it is in a polymeric form.
Postmortem paraffin-embedded tissue specimens from 15 COPD (chronic bronchitis and emphysema) cases with and without Z alpha1-AT (Glu342Lys) deficiency and from 10 cases without signs of COPD were studied. Immunohistochemistry was performed using the streptavidin-biotin method with a monoclonal ATZ11 antibody specific for polymeric alpha1-AT, and polyclonal antibodies against human alpha1-AT and neutrophil elastase. Vascular endothelium showed intense staining for alpha1-AT with the ATZ11 antibody in all cases; however, intensity of staining in patients with alpha1-AT deficiency was greater. No endothelial staining was observed with the anti-elastase antibody.
This is the first demonstration that alpha1-AT bound to the vascular endothelium of lungs is in a polymeric form, which also suggests a possible previously unknown role for polymeric alpha1-AT in vivo.
慢性阻塞性肺疾病（COPD）中肺组织的损伤可能涉及肺血管内皮细胞的逐渐丧失。已确定血浆来源的α1-抗胰蛋白酶（α1-AT）与内皮细胞结合，并且α1-AT缺乏是与α1-AT聚合和COPD发展相关的已知遗传危险因素。因此，在本研究中，我们旨在调查α1-AT是否存在于肺血管内皮上，以及它是否呈聚合形式。
研究了15例有和没有Zα1-AT（Glu342Lys）缺乏的COPD（慢性支气管炎和肺气肿）病例以及10例无COPD体征病例的死后石蜡包埋组织标本。使用链霉亲和素-生物素方法，用对聚合α1-AT特异的单克隆ATZ11抗体以及抗人α1-AT和中性粒细胞弹性蛋白酶的多克隆抗体进行免疫组织化学。在所有病例中，血管内皮用ATZ11抗体对α1-AT均显示强染色；然而，α1-AT缺乏患者的染色强度更大。抗弹性蛋白酶抗体未观察到内皮染色。
这是首次证明与肺血管内皮结合的α1-AT呈聚合形式，这也提示聚合α1-AT在体内可能有先前未知的作用。
