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Oxidative modification of albumin in the parenchymal lung tissue of current smokers with chronic obstructive pulmonary disease

Oxidative modification of albumin in the parenchymal lung tissue of current smokers with chronic obstructive pulmonary disease
Oxidative modification of albumin in the parenchymal lung tissue of current smokers with chronic obstructive pulmonary disease
Background: there is accumulating evidence that oxidative stress plays an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). One current hypothesis is that the increased oxidant burden in these patients is not adequately counterbalanced by the lung antioxidant systems.

Objective: to determine the levels of oxidised human serum albumin (HSA) in COPD lung explants and the effect of oxidation on HSA degradation using an ex vivo lung explant model.

Methods: parenchymal lung tissue was obtained from 38 patients (15F/23M) undergoing lung resection and stratified by smoking history and disease using the GOLD guidelines and the lower limit of normal for FEV1/FVC ratio. Lung tissue was homogenised and analysed by ELISA for total levels of HSA and carbonylated HSA. To determine oxidised HSA degradation lung tissue explants were incubated with either 200 ?g/ml HSA or oxidised HSA and supernatants collected at 1, 2, 4, 6, and 24 h and analysed for HSA using ELISA and immunoblot.

Results: when stratified by disease, lung tissue from GOLD II (median = 38.2 ?g/ml) and GOLD I (median = 48.4 ?g/ml) patients had lower levels of HSA compared to patients with normal lung function (median = 71.9 ?g/ml, P < 0.05). In addition the number of carbonyl residues, which is a measure of oxidation was elevated in GOLD I and II tissue compared to individuals with normal lung function (P < 0.05). When analysing smoking status current smokers had lower levels of HSA (median = 43.3 ?g/ml, P < 0.05) compared to ex smokers (median = 71.9 ?g/ml) and non-smokers (median = 71.2 ?g/ml) and significantly greater number of carbonyl residues per HSA molecule (P < 0.05). When incubated with either HSA or oxidised HSA lung tissue explants rapidly degraded the oxidised HSA but not unmodified HSA (P < 0.05).

Conclusion: we report on a reliable methodology for measuring levels of oxidised HSA in human lung tissue and cell culture supernatant. We propose that differences in the levels of oxidised HSA within lung tissue from COPD patients and current smokers provides further evidence for an oxidant/antioxidant imbalance and has important biological implications for the disease.
1465-9921
180-[1-10]
Hackett, Tillie-Louise
05158d38-5bd8-4cce-9c82-5f86ab8f2757
Scarci, Marco
5a8aeee1-d023-456d-aa4b-d66f0e78d2bf
Zheng, Lu
9391726c-5337-4871-b820-456e5010410c
Tan, Wan
42078412-3309-49ab-bdb9-d0127ffd9d29
Treasure, Tom
824addc5-0a4f-44c9-8ec2-5b2f3dda2207
Warner, Jane A.
8571b049-31bb-4a2a-a3c7-4184be20fe25
Hackett, Tillie-Louise
05158d38-5bd8-4cce-9c82-5f86ab8f2757
Scarci, Marco
5a8aeee1-d023-456d-aa4b-d66f0e78d2bf
Zheng, Lu
9391726c-5337-4871-b820-456e5010410c
Tan, Wan
42078412-3309-49ab-bdb9-d0127ffd9d29
Treasure, Tom
824addc5-0a4f-44c9-8ec2-5b2f3dda2207
Warner, Jane A.
8571b049-31bb-4a2a-a3c7-4184be20fe25

Hackett, Tillie-Louise, Scarci, Marco, Zheng, Lu, Tan, Wan, Treasure, Tom and Warner, Jane A. (2010) Oxidative modification of albumin in the parenchymal lung tissue of current smokers with chronic obstructive pulmonary disease. Respiratory Research, 11, 180-[1-10]. (doi:10.1186/1465-9921-11-180). (PMID:21176186)

Record type: Article

Abstract

Background: there is accumulating evidence that oxidative stress plays an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). One current hypothesis is that the increased oxidant burden in these patients is not adequately counterbalanced by the lung antioxidant systems.

Objective: to determine the levels of oxidised human serum albumin (HSA) in COPD lung explants and the effect of oxidation on HSA degradation using an ex vivo lung explant model.

Methods: parenchymal lung tissue was obtained from 38 patients (15F/23M) undergoing lung resection and stratified by smoking history and disease using the GOLD guidelines and the lower limit of normal for FEV1/FVC ratio. Lung tissue was homogenised and analysed by ELISA for total levels of HSA and carbonylated HSA. To determine oxidised HSA degradation lung tissue explants were incubated with either 200 ?g/ml HSA or oxidised HSA and supernatants collected at 1, 2, 4, 6, and 24 h and analysed for HSA using ELISA and immunoblot.

Results: when stratified by disease, lung tissue from GOLD II (median = 38.2 ?g/ml) and GOLD I (median = 48.4 ?g/ml) patients had lower levels of HSA compared to patients with normal lung function (median = 71.9 ?g/ml, P < 0.05). In addition the number of carbonyl residues, which is a measure of oxidation was elevated in GOLD I and II tissue compared to individuals with normal lung function (P < 0.05). When analysing smoking status current smokers had lower levels of HSA (median = 43.3 ?g/ml, P < 0.05) compared to ex smokers (median = 71.9 ?g/ml) and non-smokers (median = 71.2 ?g/ml) and significantly greater number of carbonyl residues per HSA molecule (P < 0.05). When incubated with either HSA or oxidised HSA lung tissue explants rapidly degraded the oxidised HSA but not unmodified HSA (P < 0.05).

Conclusion: we report on a reliable methodology for measuring levels of oxidised HSA in human lung tissue and cell culture supernatant. We propose that differences in the levels of oxidised HSA within lung tissue from COPD patients and current smokers provides further evidence for an oxidant/antioxidant imbalance and has important biological implications for the disease.

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Published date: 22 December 2010
Organisations: Infection Inflammation & Immunity, Biological Sciences

Identifiers

Local EPrints ID: 180889
URI: http://eprints.soton.ac.uk/id/eprint/180889
ISSN: 1465-9921
PURE UUID: 358c4b7f-d1c8-47e5-bb13-1f2191a615be

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Date deposited: 13 Apr 2011 13:50
Last modified: 14 Mar 2024 02:53

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Contributors

Author: Tillie-Louise Hackett
Author: Marco Scarci
Author: Lu Zheng
Author: Wan Tan
Author: Tom Treasure
Author: Jane A. Warner

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