Specific characteristics of immunohistochemical changes of the cellular infiltrate (the content of mucins MUC 2, 3, 4) in the mucous tunic of the bronchi in patients with chronic obstructive pulmonary disease
DOI:
https://doi.org/10.14739/2310-1237.2013.1.15304Keywords:
mucins, mucous tunic of the bronchi, inflammationAbstract
Introduction. Changes of the mucin expression by the competent cells of the bronchial mucous membrane (MM) and dyscrinia are the common evidence of the inflammatory process in case of chronic obstructive pulmonary disease (COPD) that logically substantiates the importance for the investigation of the mucin influence on the progression processes of the inflammation in the airways tract (AW). Purpose of the research. A complex study of the immunohistochemical changes of the cellular infiltration according to the mucin content MUC 2, 3, 4 in the mucous membrane of the bronchi at different variants of COPD exacerbation. Materials and Methods. An analysis of 30 case histories of patients with exacerbation of COPD undergoing inpatient treatment at the department of pulmonology was carried out. With the object of determining the degree and character of bronchial inflammation fibrobronchoscopy was carried out in all patients by means of Olympus fibrobronchoscopy. Intravital biopsy of the bronchial MM according to generally accepted technique was performed in connection with a necessity of preserving integrity of antigens in the bronchial structures for immunohistochemical investigations.
For the first time an immunohistochemical study of the expression of mucin has been carried out by means of primary monoclonal antibodies to the antigens of proteins MUC-2, MUC-3, MUC-4 in the integumentary epithelium, goblet cells, the epithelium of the mucous glands and the fusiform cells of the stroma of the mucous tunic of the bronchi in patients with chronic obstructive pulmonary disease (COPD) during an infectious and noninfectious exacerbation.
Results of the research. It has been established that during an exacerbation of chronic obstructive pulmonary disease in different types of epithelial cells of the mucous tunic of the bronchi a decline of the expression of antigens of MUC2 and MUC3 of a various degree of a marked character occurs. Synthesis of MUC 2 and MUC 3 decreases in the respiratory tract at infectious exacerbation of COPD in comparison with their expression at noninfectious exacerbation of COPD in all structures except fusiform cell of the stroma-fibroblasts. In our opinion a decrease of the mucin expression at the infectious exacerbation of COPD, most evident in the tegmental epithelium, the epithelium of the mucous glands and less in goblet cells can be explained by the influence of pathogenic microbes present in a great number on the mucous membranes and tegmental epithelium of the bronchi at infectious exacerbation of COPD. Even expression of MUC 2,3, which appears in fibroblasts of the stroma and does not depend on the variant of exacerbation of COPD is probably connected with the phenomena of an epithelial-mesenchymal transformation (EMT), when normal epithelial cells (for example, of the mucous membrane of the glands) under the influence of certain factors, for instance, TGFβ1, obtain the features of miofibroblast cells. Owing to the EMT the epithelial cells are losing intercellular ties, move to the interstitium, where obtaining a complete mesenchymal fenotype, take part in the synthesis of fibrous matrix. Conclusions. The expression of antigens MUC2 and MUC3 detected in the fusiform cells of the stroma (fibroblasts) during a COPD exacerbation enables to certify a fact of an epithelial-mesenchymal transformation, namely, a change of transformed epithelial cells, as a result of which they react differently than ordinary epithelial cells to molecular factors which play a certain role in the development of an inflammatory process and progression of fibrosis in COPD.
References
Островський М.М. Вплив базового лікування хронічного обструктивного захворювання легень на процеси морфологічної перебудови та місцевих бар’єрних факторів захисту слизових оболонок бронхів / М.М. Островський, М.О. Кулініч-Міськів // Укр. пульмон. журнал. – 2009. – №3. – С. 49–54.
Endothelial-to-mesenchymal transition contributes to cardiac fibrosis / E.M. Zeisberg // Nat Med. – 2007. – V. 13 (8). – P. 952–961.
Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation / L.A. Borthwick // Thorax. – 2009. – V. 64 (9). – P. 770–777.
Global Initiative for Chronic Obstructive Lung Disease (GOLD) / Workshop report, global strategy for diagnosis, management, and prevention of COPD. – Update 2011. Bethesda, National Institutes of Health, National Heart, Lung and Blood Institute (2007) [Електронний ресурс]. – Режим доступу: www.goldcopd.com.
Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1 / T.L. Hackett [et al.] // Am J Respir Crit Care Med. – 2009. – V. 180 (2). – P. 122–133.
Linden S.K. MUCins in the MUCosal barrier to infection / S.K. Linden // MUCosal Immunology. – 2008. – Vol. 1. – P. 183–197.
Mitchell E. Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lung of cystic fibrosis patients / E. Mitchell // Nat. Struct. Biol. – 2002. – Vol. 9. – P. 918–921.
Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients / C. Ward аt al. // Thorax. – 2005. – V. 60 (10). – P. 865–871.
Rose M.C. Respiratory tract MUCin genes and MUCin glycoproteins in health and disease / M.C. Rose, J.A. Voynow // Physiol Rev. – 2006. – Vol. 86. – P. 245–278.
Singh P.K. Cell surface-associated MUCins in signal transduction / P.K. Singh, M.A. Hollingsworth // Trends Cell Biol. – 2006. – Vol. 16. – P. 467–476.
TGF-beta1 induces human bronchial epithelial cell-to-mesenchymal transition in vitro / M. Zhang, Z. Zhang, H.Y. Pan [et al.] // Lung. – 2009. – Vol. 187 (3). – P. 187–194.
Voynow J.A. Mucins, mucus and sputum / J.A. Voynow, B.K. Rubin // Chest. – 2009. – Vol. 135. – P. 505–512.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeThe Effect of Open Access).
