The role of the SERPINs a1-antitrypsin and a1-antichymotrypsin in lung homeostasis
The role of the SERPINs a1-antitrypsin and a1-antichymotrypsin in lung homeostasis
It has been shown that there are differences in serpin levels in BAL between asthmatics and non-asthmatics at rest. Asthmatics have significantly higher levels of α1-AT but have reduced levels of α1-ACT. However, this imbalance in serpin levels did not affect total inhibitory activity and there was no difference between total inhibitory activity in asthmatics and normal BAL. Ozone inhalation results in a significant decrease in total inhibitory activity in the asthmatic lung which is mirrored by a decrease in total and active α1-AT. Ozone had no effect on serpin levels or total inhibitory activity in control subjects.
Allergen challenge results in significant increases in total inhibitory activity as well as increases in α1-AT and α1-ACT levels in BAL. It has been shown by examining the α1-AT/albumin ratio in BAL that the increase in α1-AT following allergen challenge may be partially derived from local synthesis. It has also been shown that the steroid fluticasone propionate inhibits this local production following allergen challenge.
In summary, it has been shown indirectly that asthmatics may have a decreased anti-oxidant shield in their lung, evident by decreased levels of active inhibitor following ozone inhalation. This may explain the lung damage associated with asthmatics living in highly polluted areas. Allergen challenge leads to a series of inflammatory changes that results in elevated levels of antiproteinases in the lung. A significant proportion of this may be produced locally in the lung. Finally, lung fragments and lung epithelial cells have the ability to produce significant amounts of both α1-AT and α1-AT and these inhibitors can be regulated by the proteinase elastase. This may provide a feedback loop, which is used in order to control proteolytic activity in the lung.
University of Southampton
Furr, Alex
6fc4a1c9-708f-40bc-929b-24339a3ef2f6
2001
Furr, Alex
6fc4a1c9-708f-40bc-929b-24339a3ef2f6
Furr, Alex
(2001)
The role of the SERPINs a1-antitrypsin and a1-antichymotrypsin in lung homeostasis.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
It has been shown that there are differences in serpin levels in BAL between asthmatics and non-asthmatics at rest. Asthmatics have significantly higher levels of α1-AT but have reduced levels of α1-ACT. However, this imbalance in serpin levels did not affect total inhibitory activity and there was no difference between total inhibitory activity in asthmatics and normal BAL. Ozone inhalation results in a significant decrease in total inhibitory activity in the asthmatic lung which is mirrored by a decrease in total and active α1-AT. Ozone had no effect on serpin levels or total inhibitory activity in control subjects.
Allergen challenge results in significant increases in total inhibitory activity as well as increases in α1-AT and α1-ACT levels in BAL. It has been shown by examining the α1-AT/albumin ratio in BAL that the increase in α1-AT following allergen challenge may be partially derived from local synthesis. It has also been shown that the steroid fluticasone propionate inhibits this local production following allergen challenge.
In summary, it has been shown indirectly that asthmatics may have a decreased anti-oxidant shield in their lung, evident by decreased levels of active inhibitor following ozone inhalation. This may explain the lung damage associated with asthmatics living in highly polluted areas. Allergen challenge leads to a series of inflammatory changes that results in elevated levels of antiproteinases in the lung. A significant proportion of this may be produced locally in the lung. Finally, lung fragments and lung epithelial cells have the ability to produce significant amounts of both α1-AT and α1-AT and these inhibitors can be regulated by the proteinase elastase. This may provide a feedback loop, which is used in order to control proteolytic activity in the lung.
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Published date: 2001
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Local EPrints ID: 464339
URI: http://eprints.soton.ac.uk/id/eprint/464339
PURE UUID: 2bc6c643-d8a2-4378-bde5-dec3f0d0d99b
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Date deposited: 04 Jul 2022 22:18
Last modified: 16 Mar 2024 19:25
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Author:
Alex Furr
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