Type

Journal Article

Authors

Noel G McElvaney
Shane J O'Neill
Mark L Brantly
Catherine M Greene
Matthew W Lawless
Clifford C Taggart
Alan T Mulgrew

Subjects

Biochemistry

Topics
alpha 1 antitrypsin deficiency chemistry metabolism bronchoalveolar lavage fluid lung chemotactic factors neutrophils alpha 1 antitrypsin male serpina1 protein human physiology humans middle aged adult polymers aged

Z alpha1-antitrypsin polymerizes in the lung and acts as a neutrophil chemoattractant. (2004)

Abstract Alpha1-antitrypsin (A1AT) is an abundant protein that is synthesized in the liver and is secreted into the plasma. From the plasma, A1AT diffuses into various body compartments, including the lung where it provides much of the antiprotease protection. The current understanding of the pathogenesis of emphysema in A1AT-deficient individuals focuses on the polymerization of mutant protein within the liver, which results in a deficiency of circulating A1AT and a protease-antiprotease imbalance in the lungs. In this study, we evaluated BAL fluid samples from five healthy volunteers, five individuals with ZA1AT deficiency, and an individual with the PiZZ phenotype who had received a liver transplant. We show that the lung itself is a source of A1AT. In addition, the Z protein formed in the lung polymerizes, and these polymers are detectable in lung epithelial lining fluid by enzyme-linked immunosorbent assay and Western blot analysis. Finally, we show that polymeric ZA1AT is a potent neutrophil chemoattractant that is similar to polymerized MA1AT. Our findings suggest that the polymerization of locally produced ZA1AT is a contributory factor to the lung inflammation experienced by those with A1AT deficiency and that standard antiprotease therapies may not address this problem.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Shane J O'Neill, Mark L Brantly, Catherine M Greene, Matthew W Lawless, Clifford C Taggart, Alan T Mulgrew

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Mark L Brantly
Royal College of Surgeons in Ireland
Total Publications: 3
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
5
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54