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Cells2022; 11(21); 3347; doi: 10.3390/cells11213347

Neutrophil Extracellular Vesicles and Airway Smooth Muscle Proliferation in the Natural Model of Severe Asthma in Horses.

Abstract: Extracellular vesicles (EVs) contribute to intercellular communication through the transfer of their rich cargo to recipient cells. The EVs produced by LPS-stimulated neutrophils from healthy humans and horses increase airway smooth muscle (ASM) proliferation, but the roles of neutrophil EVs in asthma are largely unexplored. The aim of this study was to determine whether neutrophil-derived EVs isolated during the remission or exacerbation of asthma influence ASM proliferation differentially. Peripheral blood neutrophils were collected during remission and exacerbation in eight horses affected by severe asthma. The cells were cultured (±LPS), and their EVs were isolated by ultracentrifugation and characterized by laser scattering microscopy and proteomic analysis. The proliferation of ASM co-incubated with EVs was monitored in real time by electrical impedance. Two proteins were significantly upregulated during disease exacerbation in neutrophil EVs (MAST4 and Lrch4), while LPS stimulation greatly altered the proteomic profile. Those changes involved the upregulation of neutrophil degranulation products, including proteases known to induce myocyte proliferation. In agreement with the proteomic results, EVs from LPS-stimulated neutrophils increased ASM proliferation, without an effect of the disease status. The inhalation of environmental LPS could contribute to asthma pathogenesis by activating neutrophils and leading to ASM hyperplasia.
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Publication Date: 2022-10-24 PubMed ID: 36359743PubMed Central: PMC9653818DOI: 10.3390/cells11213347Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 study explores the role of extracellular vesicles (EVs) produced by neutrophils in promoting airway smooth muscle (ASM) proliferation, which could have an impact on the severity of asthma in horses.

Overview of the Study

This research was conducted to investigate whether neutrophil-derived EVs, which are involved in intercellular communication, affect the proliferation of ASM in horses differently when asthma is in remission or in exacerbation. Neutrophils are a type of white blood cell that fight infections, while EVs are small particles released from cells that can carry various compounds from one cell to another. ASM cells form the muscles in the walls of the airways in the lungs. When these cells multiply excessively, they can constrict the airways and cause symptoms of asthma.

Methodology

  • Peripheral blood neutrophils were collected from eight horses affected by severe asthma during periods of remission and exacerbation.
  • The collected cells were then cultured, some with lipopolysaccharides (LPS) and some without. LPS is a molecule found on the surface of certain bacteria and is known to stimulate an immune response.
  • The EVs produced by these cultured cells were isolated using a technique called ultracentrifugation and identified using laser scattering microscopy and proteomic analysis.
  • The research team then observed the proliferation of ASM cells incubated with the EVs using electric impedance to monitor changes in real time.

Findings

  • In the course of the disease’s exacerbation, two proteins (MAST4 and Lrch4) in neutrophil EVs were found to be significantly upregulated. On the other hand, the stimulation of the neutrophils with LPS noticeably altered the proteomic profile of the EVs. This alteration saw an increase in neutrophil degranulation products, including certain proteases known to stimulate muscle cell proliferation.
  • Evidence was found to support the postulation that EVs from LPS-stimulated neutrophils improved ASM proliferation. However, the progression of the disease (whether in remission or flare-up) did not appear to affect this result.
  • The researchers propose that the inhalation of environmental LPS could potentially contribute to the pathogenesis of asthma by activating neutrophils, resulting in the over-proliferation of ASM cells.

This study sheds light on potential mechanisms of severe asthma development in horses, which could potentially inform similar studies in humans and aid in the development of new treatment strategies.

Cite This Article

APA
Mainguy-Seers S, Beaudry F, Fernandez-Prada C, Martin JG, Lavoie JP. (2022). Neutrophil Extracellular Vesicles and Airway Smooth Muscle Proliferation in the Natural Model of Severe Asthma in Horses. Cells, 11(21), 3347. https://doi.org/10.3390/cells11213347

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 11
Issue: 21
PII: 3347

Researcher Affiliations

Mainguy-Seers, Sophie
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada.
Beaudry, Francis
  • Department of Veterinary Biomedical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada.
Fernandez-Prada, Christopher
  • Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada.
Martin, James G
  • Meakins Christie Laboratories, Research Institute of the McGill University Health Centre, Montréal, QC H4A 3J1, Canada.
Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada.

MeSH Terms

  • Humans
  • Horses
  • Animals
  • Neutrophils / metabolism
  • Proteomics
  • Lipopolysaccharides / pharmacology
  • Cell Proliferation
  • Muscle, Smooth / metabolism
  • Asthma / pathology
  • Extracellular Vesicles / metabolism
  • Microtubule-Associated Proteins
  • Protein Serine-Threonine Kinases

Grant Funding

  • PJT-148807 / CIHR

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

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