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Home / Equine Research Bank / Vet J / Alveolar macrophage phenotypes in severe equine asthma.
Veterinary journal (London, England : 1997)2020; 256; 105436; doi: 10.1016/j.tvjl.2020.105436

Alveolar macrophage phenotypes in severe equine asthma.

Abstract: Because the alveolar macrophage (AM) phenotype of horses with severe equine asthma (SEA) is unknown, the cytokines expressed by M1- and M2-polarized AM were determined and the hypothesis that natural hay/straw challenge (NC) induces divergent AM phenotypes in control horses and horses with SEA was tested. Macrophages from control horses were activated either with eIFNγ + lipolysaccharide (LPS) or eIL-4 to characterize M1- or M2-polarized AM gene expression, respectively and determine the response of polarized cells to pathogen-associated molecular patterns (PAMPS): LPS, zymosan, peptidoglycan and hay dust. Subsequently, gene expression was explored in AM of control horses and horses with SEA at pasture and after NC. M1 polarization increased expression of pro-inflammatory cytokines (TNFα, IL-8, IL-12p40), IL-10, and CD80. M2 polarization increased CD206 and down-regulated arginase-II and IL-10. Expression of pro-inflammatory cytokines and CD80 in response to PAMPS was further increased by M1 pre-polarization whereas M2 pre-polarization down-regulated expression of pro-inflammatory cytokines and IL-10 but increased CD206. In horses with SEA, AMs had elevated expression of IL-10 both at pasture and after NC, but only after NC in control horses. CD206 expression increased in both groups during NC. At pasture, stimulation by PAMPS augmented expression of IL-8 and IL-10 in horses with SEA compared to control horses. NC eliminated this difference by selectively increasing expression of IL-10 in control horses. A fundamental shift in the macrophage phenotype in SEA is supported by consistently elevated production of IL-10. A similar non-canonical phenotype develops temporarily in control horses upon NC suggesting that AMs in horses with SEA have lost the ability to respond dynamically to environmental cues.
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Publication Date: 2020-02-11 PubMed ID: 32113585PubMed Central: PMC7768773DOI: 10.1016/j.tvjl.2020.105436Google Scholar: Lookup
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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.

The research investigates the phenotypes of alveolar macrophages (AM) in horses with severe equine asthma (SEA). Through various tests, it was found that horses with SEA demonstrated a unique response to environmental factors such as natural hay/straw challenge (NC), which is different from healthy, control horses. This different response is marked by a consistent increase in the production of the IL-10 cytokine in SEA horses.

Understanding Alveolar Macrophages (AM)

  • The study focuses on understanding the behavior of alveolar macrophages (AM) in horses. These are specific types of immune cells that play an important role in lung immunity.
  • Macrophages can take on different properties or ‘phenotypes.’ In this study, two phenotypes are considered: M1 (generally associated with pro-inflammatory responses) and M2 (generally associated with anti-inflammatory responses).

Characterizing AM Phenotypes

  • To better understand these phenotypes, macrophages from healthy control horses were manipulated in a lab setting to replicate M1 or M2 polarized states.
  • After polarization, the researchers exposed these cells to different pathogen-associated molecular patterns (PAMPs) which included lipopolysaccharide (LPS), zymosan, peptidoglycan, and hay dust.
  • This process helped to illuminate how each phenotype would respond to these types of stimuli. For instance, M1 polarization resulted in increased expression of pro-inflammatory cytokines, while M2 polarization led to upregulation of CD206 and downregulation of arginase-II and IL-10.

Macrophages in Horses with SEA

  • Ongoing research identified specific characteristics of AM in horses suffering from severe equine asthma (SEA).
  • Interestingly, these AM showed an elevated expression of the anti-inflammatory cytokine, IL-10, both in their natural pasture environment, and importantly, after exposure to a hay/straw challenge.
  • By contrast, control horses only showed increased IL-10 expression after the hay/straw challenge.
  • Additionally, both SEA and control horses displayed increased expression of CD206 following the hay/straw challenge.

Interpreting the Results

  • The consistent elevation of IL-10 in SEA horses provides evidence of a fundamental shift in macrophage phenotype associated with the condition.
  • Additionally, the ability of control horses to significantly elevate their IL-10 levels after a hay/straw challenge suggests that horses with SEA have somehow lost this dynamic response capability.
  • The study thus helps to highlight potential immunological changes associated with SEA which could be useful in developing new treatments or preventive measures.

Cite This Article

APA
Wilson ME, McCandless EE, Olszewski MA, Robinson NE. (2020). Alveolar macrophage phenotypes in severe equine asthma. Vet J, 256, 105436. https://doi.org/10.1016/j.tvjl.2020.105436

Publication

Veterinary journal (London, England : 1997)
ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 256
Pages: 105436
PII: S1090-0233(20)30013-7

Researcher Affiliations

Wilson, M E
  • Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.
McCandless, E E
  • Global Therapeutics Research, Zoetis, 333 Portage St, Kalamazoo, MI, 49007, USA.
Olszewski, M A
  • Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, VA Ann Arbor Healthcare System, Research Service (151), Ann Arbor, MI, 48105, USA.
Robinson, N Edward
  • Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA. Electronic address: robohand@comcast.net.

MeSH Terms

  • Animals
  • Asthma / immunology
  • Asthma / physiopathology
  • Asthma / veterinary
  • Cytokines / metabolism
  • Dust / immunology
  • Gene Expression Regulation
  • Horse Diseases / immunology
  • Horse Diseases / physiopathology
  • Horses
  • Lipopolysaccharides / pharmacology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism
  • Phenotype
  • Poaceae / immunology

Grant Funding

  • IK6 BX003615 / BLRD VA

Conflict of Interest Statement

Conflict of interest. None.

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Citations

This article has been cited 8 times.
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