Clara cell secretory protein is reduced in equine recurrent airway obstruction.
Abstract: Horses are prone to recurrent airway obstruction (RAO), an inflammatory lung disease induced by repeated exposure to environmental mold, dust, and bacterial components. Active disease manifests with mucus hyperproduction, neutrophilic inflammation, bronchoconstriction, and coughing. Chronically affected animals have lung remodeling characterized by smooth muscle hyperplasia, collagen deposition, lymphoid hyperplasia, and impaired aerobic performance. Clara cell secretory protein (CCSP) counters inflammation in the lung, hence we hypothesized that CCSP depletion is a key feature of RAO in horses. Recombinant equine CCSP and specific antiserum were produced, and percutaneous lung biopsies were obtained from 3 healthy horses and from 3 RAO-affected horses before and after induction of RAO. CCSP relative gene expression in tissue, as well as protein concentration in lung lavage fluid, was determined. Immunocytochemical analysis, using both light and immunogold ultrastructural methods, demonstrated reduced CCSP staining in lung tissue of animals with RAO. Immunogold label in Clara cell granules was less in animals with chronic RAO than in normal animals, and absent in animals that had active disease. Median lung lavage CCSP concentration was 132 and 129 ng/ml in healthy horses, and 62 and 24 ng/ml in RAO horses before and after challenge, respectively. CCSP lung gene expression was significantly higher in healthy animals than in animals with chronic RAO. Together, these preliminary findings suggest that reduced production of CCSP and subcellular changes in Clara cells are features of chronic environmentally induced lung inflammation in horses.
Publication Date: 2009-03-09 PubMed ID: 19276063DOI: 10.1354/vp.08-VP-0255-B-FLGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article explores the reduction in Clara cell secretory protein (CCSP) in horses experiencing recurrent airway obstruction (RAO), a common inflammatory lung disease in the species.
Research Context and Hypothesis
- The study revolves around understanding and investigating the incidence of Recurrent Airway Obstruction (RAO) in horses. RAO in horses is an inflammatory lung disease, which is typically induced by repeated exposure to mold, dust, and bacterial components in the environment.
- RAO has a range of symptoms, including mucus hyperproduction, neutrophilic inflammation, bronchoconstriction, coughing, and other symptoms. In chronically affected animals, it can lead to lung remodeling, characterized by hyperplasia of smooth muscles, collagen deposition, lymphoid hyperplasia, and impaired aerobic performance. This study hypothesized that a reduction in Clara cell secretory protein (CCSP) — which typically counteracts inflammation in the lung — is a key aspect of RAO in horses.
Research Methodology
- To test the hypothesis, the researchers created recombinant equine CCSP and specific antiserum. Percutaneous lung biopsies were then conducted on six horses — three of whom were healthy and three of whom were affected by RAO — both before and after the induction of RAO.
- The CCSP gene expression in tissue plus the protein concentration in lung lavage fluid were determined. Moreover, both light and immunogold ultrastructural methods were employed to conduct immunocytochemical analyses. These analyses were meant to check for any reduction in CCSP staining in lung tissue of animals with RAO.
Research Findings
- From the findings, it was noted that the immunogold label in Clara cell granules was less in animals with chronic RAO as compared to normal animals and was completely absent in animals that had active disease.
- The median lung lavage CCSP concentration in healthy horses was found to be 132 and 129 ng/ml, while in RAO horses, it was 62 and 24 ng/ml before and after challenge, respectively.
- Immunocytochemical analyses demonstrated a reduction in CCSP staining in the lung tissue of RAO-affected animals.
- Gene expression of CCSP in the lungs was significantly higher in healthy animals than in animals with chronic RAO.
Conclusion
- In conclusion, the researchers found preliminary evidence that chronic environmentally induced lung inflammation in horses is characterized by reduced CCSP production and subcellular changes in Clara cells. However, these findings are preliminary and further research is needed to fully understand this relationship.
Cite This Article
APA
Katavolos P, Ackerley CA, Viel L, Clark ME, Wen X, Bienzle D.
(2009).
Clara cell secretory protein is reduced in equine recurrent airway obstruction.
Vet Pathol, 46(4), 604-613.
https://doi.org/10.1354/vp.08-VP-0255-B-FL Publication
Researcher Affiliations
- Department of Pathobiology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
MeSH Terms
- Airway Obstruction / metabolism
- Airway Obstruction / veterinary
- Animals
- Bronchoalveolar Lavage / veterinary
- Cloning, Molecular
- DNA Primers / genetics
- Enzyme-Linked Immunosorbent Assay
- Gene Expression Regulation / physiology
- Horse Diseases / metabolism
- Horses
- Immunohistochemistry / veterinary
- Lung / metabolism
- Lung / ultrastructure
- Microscopy, Electron
- Reverse Transcriptase Polymerase Chain Reaction
- Uteroglobin / genetics
- Uteroglobin / metabolism
Citations
This article has been cited 14 times.- Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing. Animals (Basel) 2022 Mar 16;12(6).
- Kang H, Bienzle D, Lee GKC, Piché É, Viel L, Odemuyiwa SO, Beeler-Marfisi J. Flow cytometric analysis of equine bronchoalveolar lavage fluid cells in horses with and without severe equine asthma. Vet Pathol 2022 Jan;59(1):91-99.
- Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions. Front Vet Sci 2020;7:450.
- Gy C, Leclere M, Vargas A, Grimes C, Lavoie JP. Investigation of blood biomarkers for the diagnosis of mild to moderate asthma in horses. J Vet Intern Med 2019 Jul;33(4):1789-1795.
- Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma. Sci Rep 2018 Nov 6;8(1):16408.
- Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma. BMC Genomics 2017 Sep 8;18(1):708.
- Miskovic Feutz M, Couetil LL, Riley CP, Zhang X, Adamec J, Raskin RE. Secretoglobin and Transferrin Expression in Bronchoalveolar Lavage Fluid of Horses with Chronic Respiratory Disease. J Vet Intern Med 2015 Nov-Dec;29(6):1692-9.
- Sandersen C, Bienzle D, Cerri S, Franck T, Derochette S, Neven P, Mouytis-Mickalad A, Serteyn D. Effect of inhaled hydrosoluble curcumin on inflammatory markers in broncho-alveolar lavage fluid of horses with LPS-induced lung neutrophilia. Multidiscip Respir Med 2015;10(1):16.
- Senthilkumaran C, Hewson J, Ollivett TL, Bienzle D, Lillie BN, Clark M, Caswell JL. Localization of annexins A1 and A2 in the respiratory tract of healthy calves and those experimentally infected with Mannheimia haemolytica. Vet Res 2015 Feb 14;46:6.
- Côté O, Clark ME, Viel L, Labbé G, Seah SY, Khan MA, Douda DN, Palaniyar N, Bienzle D. Secretoglobin 1A1 and 1A1A differentially regulate neutrophil reactive oxygen species production, phagocytosis and extracellular trap formation. PLoS One 2014;9(4):e96217.
- Ghafouri B, Persson HL, Tagesson C. Intriguing bronchoalveolar lavage proteome in a case of pulmonary langerhans cell histiocytosis. Am J Case Rep 2013;14:129-33.
- Côté O, Lillie BN, Hayes MA, Clark ME, van den Bosch L, Katavolos P, Viel L, Bienzle D. Multiple secretoglobin 1A1 genes are differentially expressed in horses. BMC Genomics 2012 Dec 19;13:712.
- Wang XY, Keefe KM, Jensen-Taubman SM, Yang D, Yan K, Linnoila RI. Novel method for isolation of murine clara cell secretory protein-expressing cells with traces of stemness. PLoS One 2012;7(8):e43008.
- Hu J, Wan Y. Tolerogenic dendritic cells and their potential applications. Immunology 2011 Mar;132(3):307-14.
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