Oxidative Stress-induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease

被引：145

作者：

Kirkham, Paul A. ^{[1
,2
]}

Caramori, Gaetano ^{[3
,4
]}

Casolari, Paolo ^{[3
,4
]}

Papi, Alberto A. ^{[3
,4
]}

Edwards, Matt ^{[2
]}

Shamji, Betty ^{[2
]}

Triantaphyllopoulos, Kostas ^{[1
]}

Hussain, Farhana ^{[1
]}

Pinart, Mariona ^{[1
]}

Khan, Younis ^{[1
]}

Heinemann, Lucy ^{[1
]}

Stevens, Laurie ^{[1
]}

Yeadon, Mike ^{[1
]}

Barnes, Peter J. ^{[1
,5
]}

Chung, Kian F. ^{[1
,5
]}

Adcock, Ian M. ^{[1
,5
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England

[2] Novartis Inst Biomed Res, Horsham, W Sussex, England

[3] Univ Ferrara, Sect Resp Dis, I-44100 Ferrara, Italy

[4] Univ Ferrara, CEMICEF, I-44100 Ferrara, Italy

[5] Royal Brompton Resp Biomed Res Unit, London, England

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2011年 / 184卷 / 07期

基金：

英国惠康基金; 英国工程与自然科学研究理事会; 英国医学研究理事会;

关键词：

COPD; autoimmunity; oxidative stress; carbonyl; LIPID-PEROXIDATION PRODUCTS; CIGARETTE-SMOKE; INDUCED EMPHYSEMA; T-CELLS; COPD; AUTOANTIBODIES; AUTOIMMUNITY; MICE; AUTOANTIGENS; INFLAMMATION;

D O I：

10.1164/rccm.201010-1605OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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.

引用

页码：796 / 802

页数：7

共 44 条

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