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Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterised by low circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor. The most common deficiency variants are the S and Z mutations, which cause the accumulation of misfolded AAT in hepatocytes resulting in endoplasmic reticular stress and insufficient release of AAT into the circulation (<11μmol/L). This leads to liver disease, as well as an increased risk of emphysema due to unopposed proteolytic activity of neutrophil-derived serine proteinases in the lungs. AATD has been traditionally viewed as an inflammatory disorder caused directly by a proteinase-antiproteinase imbalance in the lung, but increasing evidence suggests that low AAT levels may affect other cellular functions. Recently, AAT polymers have been identified in both monocytes and macrophages from AATD patients and evidence is building that these cells may also play a role in the development of AATD lung disease. Alveolar macrophages are phagocytic cells that are important in the lung immune response but are also implicated in driving inflammation. This review explores the potential implications of monocyte and macrophage involvement in non-liver AAT synthesis and the pathophysiology of AATD lung disease.
|Number of pages||10|
|Journal||International Journal of COPD|
|Publication status||Published - 3 Dec 2020|
Bibliographical noteFunding Information:
Kylie BR Belchamber reports grants from Alpha-1 foundation, during the conduct of the study . Robert A Stockley reports personal fees from V ertex, grants and personal fees from CSL Behring, grants from Mereo biopharma and T akeda, Advisory Board for Z factor , and Chair DSMB for Kamada, during the conduct of the study . Elizabeth Sapey reports grants from Medical Research Council, grant from W ellcome T rust, grants from NIHR, grants from British Lung Foundation, grants from Alpha 1 Foundation, and grants from HDR-UK, outside the submitted work. The authors report no other potential conflicts of interest for this work.
© 2020 Belchamber et al.
- Alpha-1 antitrypsin
- Alpha-1 antitrypsin deficiency
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Health Policy
- Public Health, Environmental and Occupational Health
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- 1 Active
Does hospitalisation of older patients with severe community acquired pneumonia and sepsis lead to long term
Sapey, E., Thickett, D., Richter, A., Patel, J., Mitchell, T. & Scott, A.
1/07/19 → 30/06/23
Project: Research Councils