PMID- 33311976
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20231110
IS  - 1178-2005 (Electronic)
IS  - 1176-9106 (Print)
IS  - 1176-9106 (Linking)
VI  - 15
DP  - 2020
TI  - Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency.
PG  - 3183-3192
LID - 10.2147/COPD.S276792 [doi]
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 (<11mumol/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.
CI  - (c) 2020 Belchamber et al.
FAU - Belchamber, Kylie B R
AU  - Belchamber KBR
AUID- ORCID: 0000-0003-3241-258X
AD  - Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, 
      University of Birmingham, Birmingham, UK.
FAU - Walker, Eloise M
AU  - Walker EM
AUID- ORCID: 0000-0003-3132-8861
AD  - Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, 
      University of Birmingham, Birmingham, UK.
FAU - Stockley, Robert A
AU  - Stockley RA
AUID- ORCID: 0000-0003-3726-1207
AD  - Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, 
      University of Birmingham, Birmingham, UK.
FAU - Sapey, Elizabeth
AU  - Sapey E
AUID- ORCID: 0000-0003-3454-5482
AD  - Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, 
      University of Birmingham, Birmingham, UK.
AD  - NIHR Clinical Research Facility Birmingham, University Hospitals Birmingham NHS 
      Foundation Trust, Birmingham, UK.
LA  - eng
GR  - MR/L008335/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20201203
PL  - New Zealand
TA  - Int J Chron Obstruct Pulmon Dis
JT  - International journal of chronic obstructive pulmonary disease
JID - 101273481
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Humans
MH  - Macrophages
MH  - Monocytes
MH  - *Pulmonary Disease, Chronic Obstructive
MH  - *Pulmonary Emphysema
MH  - alpha 1-Antitrypsin/genetics
MH  - *alpha 1-Antitrypsin Deficiency/genetics
PMC - PMC7725100
OTO - NOTNLM
OT  - alpha-1 antitrypsin
OT  - alpha-1 antitrypsin deficiency
OT  - macrophage
OT  - monocyte
COIS- Kylie BR Belchamber reports grants from Alpha-1 foundation, during the conduct of 
      the study. Robert A Stockley reports personal fees from Vertex, grants and 
      personal fees from CSL Behring, grants from Mereo biopharma and Takeda, 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 Wellcome 
      Trust, 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.
EDAT- 2020/12/15 06:00
MHDA- 2021/06/29 06:00
PMCR- 2020/12/03
CRDT- 2020/12/14 10:55
PHST- 2020/08/12 00:00 [received]
PHST- 2020/10/14 00:00 [accepted]
PHST- 2020/12/14 10:55 [entrez]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2020/12/03 00:00 [pmc-release]
AID - 276792 [pii]
AID - 10.2147/COPD.S276792 [doi]
PST - epublish
SO  - Int J Chron Obstruct Pulmon Dis. 2020 Dec 3;15:3183-3192. doi: 
      10.2147/COPD.S276792. eCollection 2020.