Oxidative modification of albumin in the parenchymal lung tissue of current smokers with chronic obstructive pulmonary diseaseReportar como inadecuado

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Respiratory Research

, 11:180

First Online: 22 December 2010Received: 20 April 2010Accepted: 22 December 2010


BackgroundThere 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.

ObjectiveTo 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.

MethodsParenchymal 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 μg-ml HSA or oxidised HSA and supernatants collected at 1, 2, 4, 6, and 24 h and analysed for HSA using ELISA and immunoblot.

ResultsWhen stratified by disease, lung tissue from GOLD II median = 38.2 μg-ml and GOLD I median = 48.4 μg-ml patients had lower levels of HSA compared to patients with normal lung function median = 71.9 μg-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 μg-ml, P < 0.05 compared to ex smokers median = 71.9 μg-ml and non-smokers median = 71.2 μg-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.

ConclusionWe 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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Autor: Tillie L Hackett - Marco Scarci - Lu Zheng - Wan Tan - Tom Treasure - Jane A Warner

Fuente: https://link.springer.com/

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