PMID- 27564664
OWN - NLM
STAT- MEDLINE
DCOM- 20180105
LR  - 20220330
IS  - 2325-6621 (Electronic)
IS  - 2325-6621 (Linking)
VI  - 13 Suppl 4
DP  - 2016 Aug
TI  - The Role of Neutrophils in Alpha-1 Antitrypsin Deficiency.
PG  - S297-304
LID - 10.1513/AnnalsATS.201509-634KV [doi]
AB  - Alpha-1 antitrypsin deficiency (AATD) is characterized by low levels of 
      circulating alpha-1 antitrypsin and an increased risk for emphysema, liver 
      disease, and panniculitis. The reduced levels of alpha-1 antitrypsin in AATD 
      predispose the lung to unopposed proteolytic activity, predominantly from 
      neutrophil-derived proteases, chiefly neutrophil elastase. This leads to 
      emphysema. The mechanisms subtending the liver disease are less well understood, 
      but are probably due to a "gain-of function" inflammatory process in the liver, 
      stoked by intracellular retention of aberrantly folded alpha-1 antitrypsin. The 
      panniculitis associated with AATD is most likely due to unopposed proteolytic 
      activity in the skin. Although AATD has been traditionally viewed as a condition 
      arising from a protease-antiprotease imbalance in the lung, it is increasingly 
      recognized that AATD is an inflammatory disorder, both in the lung and in the 
      extrapulmonary manifestations associated with the condition. This inflammation is 
      predominantly neutrophil driven, and there are several alpha-1 
      antitrypsin-related mechanisms involved in potentiating this neutrophilic 
      response. The rationale for AAT augmentation therapy in AATD is classically based 
      on restoring the antiprotease balance in the lung, but its beneficial effects may 
      also be exerted systemically, further exposing the pathogenesis of AATD-related 
      disease and indicating a potential usage for alpha-1 antitrypsin in other 
      inflammatory conditions.
FAU - McCarthy, Cormac
AU  - McCarthy C
AD  - Respiratory Research Division, Department of Medicine, Royal College of Surgeons 
      in Ireland, Beaumont Hospital, Dublin, Ireland.
FAU - Reeves, Emer P
AU  - Reeves EP
AD  - Respiratory Research Division, Department of Medicine, Royal College of Surgeons 
      in Ireland, Beaumont Hospital, Dublin, Ireland.
FAU - McElvaney, Noel G
AU  - McElvaney NG
AD  - Respiratory Research Division, Department of Medicine, Royal College of Surgeons 
      in Ireland, Beaumont Hospital, Dublin, Ireland.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Ann Am Thorac Soc
JT  - Annals of the American Thoracic Society
JID - 101600811
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha 1-Antitrypsin)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
SB  - IM
MH  - Humans
MH  - Leukocyte Elastase/immunology
MH  - Liver Diseases/etiology/immunology
MH  - Lung/*immunology
MH  - Neutrophils/*immunology
MH  - Panniculitis/etiology/immunology
MH  - Pulmonary Emphysema/etiology/immunology
MH  - Tumor Necrosis Factor-alpha/immunology
MH  - alpha 1-Antitrypsin/*immunology
MH  - alpha 1-Antitrypsin Deficiency/complications/*immunology
OTO - NOTNLM
OT  - TNF-alpha
OT  - alpha-1 antitrypsin deficiency
OT  - augmentation therapy
OT  - inflammation
OT  - neutrophil elastase
EDAT- 2016/08/27 06:00
MHDA- 2018/01/06 06:00
CRDT- 2016/08/27 06:00
PHST- 2016/08/27 06:00 [entrez]
PHST- 2016/08/27 06:00 [pubmed]
PHST- 2018/01/06 06:00 [medline]
AID - 10.1513/AnnalsATS.201509-634KV [doi]
PST - ppublish
SO  - Ann Am Thorac Soc. 2016 Aug;13 Suppl 4:S297-304. doi: 
      10.1513/AnnalsATS.201509-634KV.