Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation.
Abstract: Pasture-associated severe equine asthma is a warm season, environmentally-induced respiratory disease characterized by reversible airway obstruction, persistent and non-specific airway hyper-responsiveness, and chronic neutrophilic airway inflammation. During seasonal exacerbation, signs vary from mild to life-threatening episodes of wheezing, coughing, and chronic debilitating labored breathing. In human asthma, neutrophilic airway inflammation is associated with more severe and steroid-refractory asthma phenotypes, highlighting a need to decipher the mechanistic basis of this disease characteristic. We hypothesize that the collective biological activities of proteins in bronchoalveolar lavage fluid (BALF) of horses with pasture-associated severe asthma predict changes in neutrophil functions that contribute to airway neutrophilic inflammation. Using shotgun proteomics, we identified 1,003 unique proteins in cell-free BALF from six horses experiencing asthma exacerbation and six control herdmates. Contributions of each protein to ten neutrophil functions were modeled using manual biocuration to determine each protein's net effect on the respective neutrophil functions. A total of 417 proteins were unique to asthmatic horses, 472 proteins were unique to control horses (p<0.05), and 114 proteins were common in both groups. Proteins whose biological activities are responsible for increasing neutrophil migration, chemotaxis, cell spreading, transmigration, and infiltration, which would collectively bring neutrophils to airways, were over-represented in the BALF of asthmatic relative to control horses. By contrast, proteins whose biological activities support neutrophil activation, adhesion, phagocytosis, respiratory burst, and apoptosis, which would collectively shorten neutrophil lifespan, were under-represented in BALF of asthmatic relative to control horses. Interaction networks generated using Ingenuity Pathways Analysis further support the results of our biocuration. Congruent with our hypothesis, the collective biological functions represented in differentially expressed proteins of BALF from horses with pasture-associated severe asthma support neutrophilic airway inflammation. This illustrates the utility of systems modeling to organize functional genomics data in a manner that characterizes complex molecular events associated with clinically relevant disease.
Publication Date: 2019-05-02 PubMed ID: 31119093PubMed Central: PMC6504673DOI: 10.2147/VMRR.S194427Google Scholar: Lookup
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- Journal Article
Summary
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The research study is focused on understanding the molecular mechanisms behind pasture-associated severe equine asthma to shed light on neutrophilic airway inflammation. The authors applied proteomic analysis to bronchoalveolar lavage fluid from asthmatic and non-asthmatic horses and found that certain proteins associated with increased neutrophil activity were more prevalent in the asthmatic subjects.
Objective and Hypothesis
- The research article revolves around studying pasture-associated severe equine asthma, a respiratory disease occurring in warm seasons causing breathing difficulties in horses due to airway obstruction and chronic inflammation.
- The study authors proposed a hypothesis that the proteins found in the bronchoalveolar lavage fluid (BALF) of asthmatic horses play a significant role in the neutrophil activities, ultimately contributing to the overall airway inflammation.
Method of Data Collection
- The researchers used shotgun proteomics to identify unique proteins present in the BALF of the affected horses and healthy counterparts, ultimately cataloging 1,003 individual proteins.
- The team then applied manual biocuration to determine the net effects of these proteins on various neutrophil functions. This predictive model was designed to understand changes in these functions related to asthma.
Significant Findings
- A total of 417 proteins were unique to the affected horses, while 472 proteins were only found in the control group; only 114 proteins were shared by both groups.
- It was noted that the proteins associated with the processes increasing neutrophil activities (migration, chemotaxis, spreading, transmigration, infiltration) were over-represented in asthmatic horses.
- In contrast, proteins promoting neutrophil activation, adhesion, phagocytosis, respiratory burst, and apoptosis (which arguably shorten neutrophil lifespan) were found to have less representation in the BALF of asthmatic horses.
Impact of these findings
- The model and results supported the initial hypothesis, indicating that there are indeed differences in the protein activities impacting neutrophil functions contributing to airway inflammation in horses with asthma when compared to healthy horses.
- This research illustrates the importance of using systems modeling for understanding the roles of various proteins in disease processes, enabling a more nuanced approach to devising potential treatment options.
Cite This Article
APA
Bright LA, Dittmar W, Nanduri B, McCarthy FM, Mujahid N, Costa LR, Burgess SC, Swiderski CE.
(2019).
Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation.
Vet Med (Auckl), 10, 43-63.
https://doi.org/10.2147/VMRR.S194427 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA.
- Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA.
- School of Animal Comparative and Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85721, USA.
- Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA.
- Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA.
- School of Animal Comparative and Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85721, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA.
Conflict of Interest Statement
The authors report no conflicts of interest in this work.
References
This article includes 123 references
Citations
This article has been cited 6 times.- Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL. Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro.. Int J Mol Sci 2022 Aug 23;23(17).
- 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).
- Karagianni AE, Kurian D, Cillán-Garcia E, Eaton SL, Wishart TM, Pirie RS. Training associated alterations in equine respiratory immunity using a multiomics comparative approach.. Sci Rep 2022 Jan 10;12(1):427.
- Karagianni AE, Eaton SL, Kurian D, Cillán-Garcia E, Twynam-Perkins J, Raper A, Wishart TM, Pirie RS. Application across species of a one health approach to liquid sample handling for respiratory based -omics analysis.. Sci Rep 2021 Jul 12;11(1):14292.
- Degroote RL, Weigand M, Hauck SM, Deeg CA. IL8 and PMA Trigger the Regulation of Different Biological Processes in Granulocyte Activation.. Front Immunol 2019;10:3064.
- Sheats MK, Davis KU, Poole JA. Comparative Review of Asthma in Farmers and Horses.. Curr Allergy Asthma Rep 2019 Oct 10;19(11):50.
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