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Frontiers in veterinary science2023; 9; 997139; doi: 10.3389/fvets.2022.997139

Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma.

Abstract: Equine asthma is a naturally occurring lung disease characterized by chronic, partially reversible airway obstruction, pulmonary remodeling, and lower airway inflammation. Asthma is currently divided into two major groups, mild to moderate asthma (mEA) and severe asthma (sEA), but further subtyping by phenotype (i.e., clinical presentation) and/or endotype (i.e., cellular mechanisms) may be warranted. For this study, we were interested in further investigation of cellular and inflammatory characteristics of EA, including airway mast cells. The purpose of this study was to: (1) compare mast cell protease mRNA expression between healthy and asthmatic horses, (2) analyze the cytokine profile present in BALF of currently defined equine asthma groups, and (3) use these data to evaluate potential biomarkers of defined asthma groups. We hypothesized that there would be significant differences in the cellular mast cell phenotypes (i.e., mucosal vs. connective tissue) and cytokine profiles in the BALF of asthmatic vs. healthy horses and across asthma groups. We assert these characteristics may inform additional subtypes of equine asthma. Adult horses were recruited from the institution's teaching herd and clinical caseload. Mast cell protease gene expression of the BALF cellular component and multiplex bead immunoassay for cytokine concentrations in the BALF supernatant were investigated. Airway mast cells primarily expressed tryptase, with low levels of chymase. No significant changes in protease expression were detected across groups. Horses with severe asthma had increased TNF-α, CXCL-8, and IFN-γ concentrations in BALF supernatant. Multidimensional analysis demonstrated healthy and mEA horses have overlapping characteristics, with sEA separating from the other groups. This difference was primarily due to BALF neutrophil and lymphocyte concentrations. These study results further inform understanding of EA immunopathology, and future studies designed to investigate asthma phenotypes and endotypes. Ultimately, a better understanding of these groups could help identify novel therapeutic strategies.
Publication Date: 2023-01-11 PubMed ID: 36713876PubMed Central: PMC9875299DOI: 10.3389/fvets.2022.997139Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the cellular and inflammatory characteristics of Equine Asthma (EA), a common chronic inflammatory disease of the lung in horses. This research checks for differences in the airway mast cell phenotypes, levels of pro-inflammatory cytokines, and tries to understand their role in the presentation of the disease, which can potentially lead to the identification of new treatment strategies.

Research Methodology and Purpose

  • The study aims to understand the differences in mast cell protease mRNA expression between healthy and asthmatic horses.
  • It also aims to analyze the cytokine profiles in Bronchoalveolar Lavage Fluid (BALF) of horses with different severity of equine asthma.
  • The study hypothesized that significant differences would be observed in the cellular mast cell phenotypes and cytokine profiles in the BALF of asthmatic vs. healthy horses, and between horses with different grades of asthma.
  • The researchers believed the findings may lead to further categorization of EA and potentially pave the way for novel targeted therapies.

Materials and Approach

  • Adult horses were chosen for the study from the institution’s teaching herd and clinical caseload.
  • The researchers analyzed the gene expression of mast cell protease in the BALF cells, and checked the cytokine concentrations in the BALF supernatant using a multiplex bead immunoassay.

Research Outcomes

  • The primary expression in airway mast cells was of tryptase, with chymase present in low quantities. No significant alterations in protease expression were seen across the different test groups.
  • Severely asthmatic horses had elevated concentrations of cytokines TNF-α, CXCL-8, and IFN-γ in the BALF supernatant.
  • The countrywide analysis showed overlapping characteristics between healthy horses and horses with mild to moderate asthma, with severely asthmatic horses forming a separate group. This distinction was primarily due to differences in BALF neutrophil and lymphocyte concentrations.
  • The results provide crucial insights into EA’s immunopathology and will guide future research to explore asthma phenotypes and cellular mechanisms further. This understanding could assist in identifying new therapeutic strategies to manage EA better.

Cite This Article

APA
Woodrow JS, Hines M, Sommardahl C, Flatland B, Lo Y, Wang Z, Sheats MK, Lennon EM. (2023). Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma. Front Vet Sci, 9, 997139. https://doi.org/10.3389/fvets.2022.997139

Publication

ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 9
Pages: 997139
PII: 997139

Researcher Affiliations

Woodrow, Jane S
  • Department of Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United States.
  • Department of Clinical Sciences and Advanced Medicine, College of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Hines, Melissa
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United States.
Sommardahl, Carla
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United States.
Flatland, Bente
  • Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United States.
Lo, Yancy
  • Bioinformatics Core, Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, United States.
Wang, Zhiping
  • Bioinformatics Core, Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, United States.
Sheats, Mary Katie
  • Department of Clinical Sciences, Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Lennon, Elizabeth M
  • Department of Clinical Sciences and Advanced Medicine, College of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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