title: Polymerized alpha-antitrypsin is present on lung vascular endothelium. New insights into the biological significance of alpha-antitrypsin polymerization.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathology, University Hospital Malmo, Malmö, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Aldonyte
authors.forename: L
authors.initials: L
authors.lastname: Jansson
authors.forename: O
authors.initials: O
authors.lastname: Ljungberg
authors.forename: S
authors.initials: S
authors.lastname: Larsson
authors.forename: S
authors.initials: S
authors.lastname: Janciauskiene
mesh_terms: D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000473:pathology; D011108:Polymers; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D011108:Polymers; D000515:alpha 1-Antitrypsin