Polymerized α1-antitrypsin is present on lung vascular endothelium.: New insights into the biological significance of α1-antitrypsin polymerization

Aims: 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 (alpha(1)-AT) derived from plasma has been identified, and alpha(1)-AT deficiency is a known genetic risk factor associated with alpha(1)-AT polymerization and COPD development. Therefore, in the present study we aimed to investigate if alpha(1)-AT is present on the lung vascular endothelium, and if it is in a polymeric form. Methods and results: Postmortem paraffin-embedded tissue specimens from 15 COPD (chronic bronchitis and emphysema) cases with and without Z alpha(1)-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 alpha(1)-AT, and polyclonal antibodies against human alpha(1)-AT and neutrophil elastase. Vascular endothelium showed intense staining for alpha(1)-AT with the ATZ11 antibody in all cases; however, intensity of staining in patients with alpha(1)-AT deficiency was greater. No endothelial staining was observed with the anti-elastase antibody. Conclusions: This is the first demonstration that alpha(1)-AT bound to the vascular endothelium of lungs is in a polymeric form, which also suggests a possible previously unknown role for polymeric alpha(1)-AT in vivo.