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

By Tillie-Louise Hackett, Marco Scarci, Lu Zheng, Wan Tan, Tom Treasure and Jane A. Warner

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.<br/><br/>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.<br/><br/>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.<br/><br/>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 &lt; 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 &lt; 0.05). When analysing smoking status current smokers had lower levels of HSA (median = 43.3 ?g/ml, P &lt; 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 &lt; 0.05). When incubated with either HSA or oxidised HSA lung tissue explants rapidly degraded the oxidised HSA but not unmodified HSA (P &lt; 0.05).<br/><br/>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.<br/

Topics: RC0254
Year: 2010
OAI identifier: oai:eprints.soton.ac.uk:180889
Provided by: e-Prints Soton

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