Polymerized alpha-antitrypsin is present on lung vascular endothelium. New insights into the biological significance of alpha-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 (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. METHODS AND RESULTS 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. CONCLUSIONS 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.