Monocytes and macrophages in alpha-1 antitrypsin deficiency

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Monocytes and macrophages in alpha-1 antitrypsin deficiency. / Belchamber, Kylie B. R.; Walker, Eloise M.; Stockley, Robert A.; Sapey, Elizabeth.

In: International Journal of COPD, Vol. 15, 03.12.2020, p. 3183-3192.

Research output: Contribution to journalReview articlepeer-review

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@article{712eecc988cb4dc98c7fba074ae1eb25,
title = "Monocytes and macrophages in alpha-1 antitrypsin deficiency",
abstract = "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 = "Alpha-1 antitrypsin, Alpha-1 antitrypsin deficiency, Macrophage, Monocyte",
author = "Belchamber, {Kylie B. R.} and Walker, {Eloise M.} and Stockley, {Robert A.} and Elizabeth Sapey",
note = "Funding 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. Publisher Copyright: {\textcopyright} 2020 Belchamber et al.",
year = "2020",
month = dec,
day = "3",
doi = "10.2147/COPD.S276792",
language = "English",
volume = "15",
pages = "3183--3192",
journal = "International journal of chronic obstructive pulmonary disease",
issn = "1176-9106",
publisher = "Dove Medical Press",

}

RIS

TY - JOUR

T1 - Monocytes and macrophages in alpha-1 antitrypsin deficiency

AU - Belchamber, Kylie B. R.

AU - Walker, Eloise M.

AU - Stockley, Robert A.

AU - Sapey, Elizabeth

N1 - Funding 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. Publisher Copyright: © 2020 Belchamber et al.

PY - 2020/12/3

Y1 - 2020/12/3

N2 - 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.

AB - 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.

KW - Alpha-1 antitrypsin

KW - Alpha-1 antitrypsin deficiency

KW - Macrophage

KW - Monocyte

UR - http://www.scopus.com/inward/record.url?scp=85097601502&partnerID=8YFLogxK

U2 - 10.2147/COPD.S276792

DO - 10.2147/COPD.S276792

M3 - Review article

C2 - 33311976

AN - SCOPUS:85097601502

VL - 15

SP - 3183

EP - 3192

JO - International journal of chronic obstructive pulmonary disease

JF - International journal of chronic obstructive pulmonary disease

SN - 1176-9106

ER -