Dataset Information

Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease.

ABSTRACT:

Rationale

There is increasing evidence for the presence of autoantibodies in chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an essential component in COPD pathogenesis and can lead to increased levels of highly reactive carbonyls in the lung, which could result in the formation of highly immunogenic carbonyl adducts on "self" proteins.

Objectives

To determine the presence of autoantibodies to carbonyl-modified protein in patients with COPD and in a murine model of chronic ozone exposure. To assess the extent of activated immune responses toward carbonyl-modified proteins.

Methods

Blood and peripheral lung were taken from patients with COPD, age-matched smokers, and nonsmokers with normal lung function, as well as patients with severe persistent asthma. Mice were exposed to ambient air or ozone for 6 weeks. Antibody titers were measured by ELISA, activated compliment deposition by immunohistochemistry, and cellular activation by ELISA and fluorescence-activated cell sorter.

Measurements and main results

Antibody titer against carbonyl-modified self-protein was significantly increased in patients with Global Initiative for Chronic Obstructive Lung Disease stage III COPD compared with control subjects. Antibody levels inversely correlated with disease severity and showed a prevalence toward an IgG1 isotype. Deposition of activated complement in the vessels of COPD lung as well as autoantibodies against endothelial cells were also observed. Ozone-exposed mice similarly exhibited increased antibody titers to carbonyl-modified protein, as well as activated antigen-presenting cells in lung tissue and splenocytes sensitized to activation by carbonyl-modified protein.

Conclusions

Carbonyl-modified proteins, arising as a result of oxidative stress, promote antibody production, providing a link by which oxidative stress could drive an autoimmune response in COPD.

SUBMITTER: Kirkham PA

PROVIDER: S-EPMC3398415 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Publications

Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease.

Kirkham Paul A PA Caramori Gaetano G Casolari Paolo P Papi Alberto A AA Edwards Matt M Shamji Betty B Triantaphyllopoulos Kostas K Hussain Farhana F Pinart Mariona M Khan Younis Y Heinemann Lucy L Stevens Laurie L Yeadon Mike M Barnes Peter J PJ Chung Kian F KF Adcock Ian M IM

American journal of respiratory and critical care medicine 20111001 7

<h4>Rationale</h4>There is increasing evidence for the presence of autoantibodies in chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an essential component in COPD pathogenesis and can lead to increased levels of highly reactive carbonyls in the lung, which could result in the formation of highly immunogenic carbonyl adducts on "self" proteins.<h4>Objectives</h4>To determine the presence of autoantibodies to carbonyl-modified protein in patients with COPD and in a murin ...[more]

PMID: 21965015

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Dataset Information

Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease.

Similar Datasets

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