Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation

Lauren A Bright,1 Wellesley Dittmar,1 Bindu Nanduri,2 Fiona M McCarthy,3 Nisma Mujahid,2 Lais RR Costa,2 Shane C Burgess,3 Cyprianna E Swiderski11Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA; 2Department of Basic Sciences, C...

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Autores principales:	Bright LA, Dittmar W, Nanduri B, McCarthy FM, Mujahid N, Costa LRR, Burgess SC, Swiderski CE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	pasture-associated severe equine asthma Equus caballus horse proteomics neutrophil functional genomics Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/9db6805f014a4b7f80bc7e0b9995a9dd
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spelling	oai:doaj.org-article:9db6805f014a4b7f80bc7e0b9995a9dd2021-12-02T13:15:15ZModeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation2230-2034https://doaj.org/article/9db6805f014a4b7f80bc7e0b9995a9dd2019-05-01T00:00:00Zhttps://www.dovepress.com/modeling-the-pasture-associated-severe-equine-asthma-bronchoalveolar-l-peer-reviewed-article-VMRRhttps://doaj.org/toc/2230-2034Lauren A Bright,1 Wellesley Dittmar,1 Bindu Nanduri,2 Fiona M McCarthy,3 Nisma Mujahid,2 Lais RR Costa,2 Shane C Burgess,3 Cyprianna E Swiderski11Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA; 2Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA; 3School of Animal Comparative and Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85721, USABackground: 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.Purpose: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: pasture-associated severe equine asthma, Equus caballus, horse, proteomics, neutrophil functional genomicsBright LADittmar WNanduri BMcCarthy FMMujahid NCosta LRRBurgess SCSwiderski CEDove Medical Pressarticlepasture-associated severe equine asthmaEquus caballushorseproteomicsneutrophil functional genomicsVeterinary medicineSF600-1100ENVeterinary Medicine: Research and Reports, Vol Volume 10, Pp 43-63 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	pasture-associated severe equine asthma Equus caballus horse proteomics neutrophil functional genomics Veterinary medicine SF600-1100
spellingShingle	pasture-associated severe equine asthma Equus caballus horse proteomics neutrophil functional genomics Veterinary medicine SF600-1100 Bright LA Dittmar W Nanduri B McCarthy FM Mujahid N Costa LRR Burgess SC Swiderski CE Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation
description	Lauren A Bright,1 Wellesley Dittmar,1 Bindu Nanduri,2 Fiona M McCarthy,3 Nisma Mujahid,2 Lais RR Costa,2 Shane C Burgess,3 Cyprianna E Swiderski11Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA; 2Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA; 3School of Animal Comparative and Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85721, USABackground: 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.Purpose: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: pasture-associated severe equine asthma, Equus caballus, horse, proteomics, neutrophil functional genomics
format	article
author	Bright LA Dittmar W Nanduri B McCarthy FM Mujahid N Costa LRR Burgess SC Swiderski CE
author_facet	Bright LA Dittmar W Nanduri B McCarthy FM Mujahid N Costa LRR Burgess SC Swiderski CE
author_sort	Bright LA
title	Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation
title_short	Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation
title_full	Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation
title_fullStr	Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation
title_full_unstemmed	Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation
title_sort	modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/9db6805f014a4b7f80bc7e0b9995a9dd
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Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation

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