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Polymerized α 1 ‐antitrypsin is present on lung vascular endothelium. New insights into the biological significance of α 1 ‐antitrypsin polymerization
Author(s) -
Aldonyte R,
Jansson L,
Ljungberg O,
Larsson S,
Janciauskiene S
Publication year - 2004
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2004.02021.x
Subject(s) - pathology , endothelium , copd , lung , immunohistochemistry , neutrophil elastase , staining , chronic bronchitis , elastase , medicine , biology , immunology , chemistry , inflammation , biochemistry , enzyme
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 α1‐antitrypsin (α 1 ‐AT) derived from plasma has been identified, and α 1 ‐AT deficiency is a known genetic risk factor associated with α 1 ‐AT polymerization and COPD development. Therefore, in the present study we aimed to investigate if α 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 α 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 α 1 ‐AT, and polyclonal antibodies against human α 1 ‐AT and neutrophil elastase. Vascular endothelium showed intense staining for α 1 ‐AT with the ATZ11 antibody in all cases; however, intensity of staining in patients with α 1 ‐AT deficiency was greater. No endothelial staining was observed with the anti‐elastase antibody. Conclusions: This is the first demonstration that α 1 ‐AT bound to the vascular endothelium of lungs is in a polymeric form, which also suggests a possible previously unknown role for polymeric α 1 ‐AT in vivo .