| Bronchial secretory immunoglobulin a deficiency correlates with airway inflammation and progression of chronic obstructive pulmonary disease. | |
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MedLine Citation:
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PMID: 21512171 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Although airway inflammation can persist for years after smoking cessation in patients with chronic obstructive pulmonary disease (COPD), the mechanisms of persistent inflammation are largely unknown. OBJECTIVES: We investigated relationships between bronchial epithelial remodeling, polymeric immunoglobulin receptor (pIgR) expression, secretory IgA (SIgA), airway inflammation, and mural remodeling in COPD. METHODS: Lung tissue specimens and bronchoalveolar lavage were obtained from lifetime nonsmokers and former smokers with or without COPD. Epithelial structural changes were quantified by morphometric analysis. Expression of pIgR was determined by immunostaining and real-time polymerase chain reaction. Immunohistochemistry was performed for IgA, CD4 and CD8 lymphocytes, and cytomegalovirus and Epstein-Barr virus antigens. Total IgA and SIgA were measured by ELISA and IgA transcytosis was studied using cultured human bronchial epithelial cells. MEASUREMENTS AND MAIN RESULTS: Areas of bronchial mucosa covered by normal pseudostratified ciliated epithelium were characterized by pIgR expression with SIgA present on the mucosal surface. In contrast, areas of bronchial epithelial remodeling had reduced pIgR expression, localized SIgA deficiency, and increased CD4(+) and CD8(+) lymphocyte infiltration. In small airways (<2 mm), these changes were associated with presence of herpesvirus antigens, airway wall remodeling, and airflow limitation in patients with COPD. Patients with COPD had reduced SIgA in bronchoalveolar lavage. Air-liquid interface epithelial cell cultures revealed that complete epithelial differentiation was required for normal pIgR expression and IgA transcytosis. CONCLUSIONS: Our findings indicate that epithelial structural abnormalities lead to localized SIgA deficiency in COPD airways. Impaired mucosal immunity may contribute to persistent airway inflammation and progressive airway remodeling in COPD. |
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Authors:
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Vasiliy V Polosukhin; Justin M Cates; William E Lawson; Rinat Zaynagetdinov; Aaron P Milstone; Pierre P Massion; Sebahat Ocak; Lorraine B Ware; Jae Woo Lee; Russell P Bowler; Alexey V Kononov; Scott H Randell; Timothy S Blackwell |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-04-21 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 184 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-01 Completed Date: 2011-09-30 Revised Date: 2012-04-20 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 317-27 Citation Subset: AIM; IM |
Affiliation:
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Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA. vasiliy.v.polosukhin@vanderbilt.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Airway Remodeling
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immunology* Bronchi / pathology, physiopathology, virology Cytomegalovirus / isolation & purification Herpesvirus 4, Human / isolation & purification Humans Immunoglobulin A, Secretory / analysis, immunology* Inflammation / immunology, physiopathology Pulmonary Disease, Chronic Obstructive / immunology*, physiopathology Receptors, Polymeric Immunoglobulin / immunology* Respiratory System / immunology Smoking / adverse effects*, immunology Time |
| Grant Support | |
ID/Acronym/Agency:
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DK065988/DK/NIDDK NIH HHS; HL080322/HL/NHLBI NIH HHS; HL085406/HL/NHLBI NIH HHS; HL088263/HL/NHLBI NIH HHS; UL1PR024975-01/PR/OCPHP CDC HHS |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin A, Secretory; 0/Receptors, Polymeric Immunoglobulin |
| Comments/Corrections | |
Comment In:
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Am J Respir Crit Care Med. 2012 Mar 15;185(6):686-7
[PMID:
22422908
]
Am J Respir Crit Care Med. 2011 Aug 1;184(3):285-7 [PMID: 21804117 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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