Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency
Kylie BR Belchamber,1 Eloise M Walker,1 Robert A Stockley,1 Elizabeth Sapey1,2 1Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 2NIHR Clinical Research Facility Birmingham, University Hospitals Birmingham NHS Foundation Trust, Bir...
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doaj-f0e3839a57844080be1a1341379066f62020-12-03T20:15:52ZengDove Medical PressInternational Journal of COPD1178-20052020-12-01Volume 153183319259971Monocytes and Macrophages in Alpha-1 Antitrypsin DeficiencyBelchamber KBRWalker EMStockley RASapey EKylie BR Belchamber,1 Eloise M Walker,1 Robert A Stockley,1 Elizabeth Sapey1,2 1Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 2NIHR Clinical Research Facility Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKCorrespondence: Kylie BR BelchamberBirmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UKEmail k.belchamber@bham.ac.ukAbstract: 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.Keywords: monocyte, macrophage, alpha-1 antitrypsin, alpha-1 antitrypsin deficiencyhttps://www.dovepress.com/monocytes-and-macrophages-in-alpha-1-antitrypsin-deficiency-peer-reviewed-article-COPDmonocyte macrophage alpha-1 antitrypsin alpha-1 antitrypsin deficiency |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Belchamber KBR Walker EM Stockley RA Sapey E |
spellingShingle |
Belchamber KBR Walker EM Stockley RA Sapey E Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency International Journal of COPD monocyte macrophage alpha-1 antitrypsin alpha-1 antitrypsin deficiency |
author_facet |
Belchamber KBR Walker EM Stockley RA Sapey E |
author_sort |
Belchamber KBR |
title |
Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency |
title_short |
Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency |
title_full |
Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency |
title_fullStr |
Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency |
title_full_unstemmed |
Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency |
title_sort |
monocytes and macrophages in alpha-1 antitrypsin deficiency |
publisher |
Dove Medical Press |
series |
International Journal of COPD |
issn |
1178-2005 |
publishDate |
2020-12-01 |
description |
Kylie BR Belchamber,1 Eloise M Walker,1 Robert A Stockley,1 Elizabeth Sapey1,2 1Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 2NIHR Clinical Research Facility Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKCorrespondence: Kylie BR BelchamberBirmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UKEmail k.belchamber@bham.ac.ukAbstract: 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.Keywords: monocyte, macrophage, alpha-1 antitrypsin, alpha-1 antitrypsin deficiency |
topic |
monocyte macrophage alpha-1 antitrypsin alpha-1 antitrypsin deficiency |
url |
https://www.dovepress.com/monocytes-and-macrophages-in-alpha-1-antitrypsin-deficiency-peer-reviewed-article-COPD |
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