FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
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.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Get Full Text
Publication Date: 2020-02-11 PubMed ID: 32113585PubMed Central: PMC7768773DOI: 10.1016/j.tvjl.2020.105436Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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.

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.

References

This article includes 24 references
  1. Arora S, Dev K, Agarwal B, Das P, Syed MA. Macrophages: Their role, activation and polarization in pulmonary diseases.. Immunobiology 2018 Apr-May;223(4-5):383-396.
    pmc: PMC7114886pubmed: 29146235doi: 10.1016/j.imbio.2017.11.001google scholar: lookup
  2. Behan AL, Hauptman JG, Robinson NE. Telemetric analysis of breathing pattern variability in recurrent airway obstruction (heaves)-affected horses.. Am J Vet Res 2013 Jun;74(6):925-33.
    pubmed: 23718662doi: 10.2460/ajvr.74.6.925google scholar: lookup
  3. Bond S, Léguillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS. Equine asthma: Integrative biologic relevance of a recently proposed nomenclature.. J Vet Intern Med 2018 Nov;32(6):2088-2098.
    pmc: PMC6271326pubmed: 30294851doi: 10.1111/jvim.15302google scholar: lookup
  4. Bullone M, Lavoie JP. Asthma "of horses and men"--how can equine heaves help us better understand human asthma immunopathology and its functional consequences?. Mol Immunol 2015 Jul;66(1):97-105.
    pubmed: 25547716doi: 10.1016/j.molimm.2014.12.005google scholar: lookup
  5. Davis MJ, Tsang TM, Qiu Y, Dayrit JK, Freij JB, Huffnagle GB, Olszewski MA. Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in Cryptococcus neoformans infection.. mBio 2013 Jun 18;4(3):e00264-13.
    pmc: PMC3684832pubmed: 23781069doi: 10.1128/mBio.00264-13google scholar: lookup
  6. Gazi U, Martinez-Pomares L. Influence of the mannose receptor in host immune responses.. Immunobiology 2009;214(7):554-61.
    pubmed: 19162368doi: 10.1016/j.imbio.2008.11.004google scholar: lookup
  7. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions.. Immunity 2010 May 28;32(5):593-604.
    pubmed: 20510870doi: 10.1016/j.immuni.2010.05.007google scholar: lookup
  8. Joubert P, Cordeau ME, Lavoie JP. Cytokine mRNA expression of pulmonary macrophages varies with challenge but not with disease state in horses with heaves or in controls.. Vet Immunol Immunopathol 2011 Aug 15;142(3-4):236-42.
    pubmed: 21664702doi: 10.1016/j.vetimm.2011.05.022google scholar: lookup
  9. Karagianni AE, Kapetanovic R, McGorum BC, Hume DA, Pirie SR. The equine alveolar macrophage: functional and phenotypic comparisons with peritoneal macrophages.. Vet Immunol Immunopathol 2013 Oct 1;155(4):219-28.
    pmc: PMC3795452pubmed: 23978307doi: 10.1016/j.vetimm.2013.07.003google scholar: lookup
  10. Karagianni AE, Kapetanovic R, Summers KM, McGorum BC, Hume DA, Pirie RS. Comparative transcriptome analysis of equine alveolar macrophages.. Equine Vet J 2017 May;49(3):375-382.
    pmc: PMC5412682pubmed: 27096353doi: 10.1111/evj.12584google scholar: lookup
  11. Laan TT, Bull S, Pirie RS, Fink-Gremmels J. Evaluation of cytokine production by equine alveolar macrophages exposed to lipopolysaccharide, Aspergillus fumigatus, and a suspension of hay dust.. Am J Vet Res 2005 Sep;66(9):1584-9.
    pubmed: 16261833doi: 10.2460/ajvr.2005.66.1584google scholar: lookup
  12. Laan TT, Bull S, Pirie R, Fink-Gremmels J. The role of alveolar macrophages in the pathogenesis of recurrent airway obstruction in horses.. J Vet Intern Med 2006 Jan-Feb;20(1):167-74.
    pubmed: 16496937doi: 10.1892/0891-6640(2006)20[167:troami]2.0.co;2google scholar: lookup
  13. Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, David F, Martin JG, Lavoie JP. Effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma.. Am J Respir Cell Mol Biol 2011 Jul;45(1):181-7.
    pubmed: 20935189doi: 10.1165/rcmb.2010-0300OCgoogle scholar: lookup
  14. Lee CG, Homer RJ, Cohn L, Link H, Jung S, Craft JE, Graham BS, Johnson TR, Elias JA. Transgenic overexpression of interleukin (IL)-10 in the lung causes mucus metaplasia, tissue inflammation, and airway remodeling via IL-13-dependent and -independent pathways.. J Biol Chem 2002 Sep 20;277(38):35466-74.
    pubmed: 12107190doi: 10.1074/jbc.M206395200google scholar: lookup
  15. Lugo J, Harkema JR, deFeijter-Rupp H, Bartner L, Boruta D, Robinson NE. Airway inflammation is associated with mucous cell metaplasia and increased intraepithelial stored mucosubstances in horses.. Vet J 2006 Sep;172(2):293-301.
    pubmed: 15925524doi: 10.1016/j.tvjl.2005.04.018google scholar: lookup
  16. Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling.. J Pathol 2013 Jan;229(2):176-85.
    pubmed: 23096265doi: 10.1002/path.4133google scholar: lookup
  17. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation.. Nat Rev Immunol 2008 Dec;8(12):958-69.
    pmc: PMC2724991pubmed: 19029990doi: 10.1038/nri2448google scholar: lookup
  18. Murray PJ. The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription.. Proc Natl Acad Sci U S A 2005 Jun 14;102(24):8686-91.
    pmc: PMC1150817pubmed: 15937121doi: 10.1073/pnas.0500419102google scholar: lookup
  19. Pirie RS. Recurrent airway obstruction: a review.. Equine Vet J 2014 May;46(3):276-88.
    pubmed: 24164473doi: 10.1111/evj.12204google scholar: lookup
  20. Pirie RS, Dixon PM, Collie DD, McGorum BC. Pulmonary and systemic effects of inhaled endotoxin in control and heaves horses.. Equine Vet J 2001 May;33(3):311-8.
    pubmed: 11352355doi: 10.2746/042516401776249732google scholar: lookup
  21. Pirie RS, McLachlan G, McGorum BC. Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 1: Preparation and composition of HDS.. Equine Vet J 2002 Jul;34(4):332-6.
    pubmed: 12117103doi: 10.2746/042516402776249092google scholar: lookup
  22. Robinson NE. International Workshop on Equine Chronic Airway Disease. Michigan State University 16-18 June 2000.. Equine Vet J 2001 Jan;33(1):5-19.
    pubmed: 11191611doi: 10.2746/042516401776767412google scholar: lookup
  23. Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation.. J Exp Med 1992 Jul 1;176(1):287-92.
    pmc: PMC2119288pubmed: 1613462doi: 10.1084/jem.176.1.287google scholar: lookup
  24. Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Fortes B, Thompson R, Linden J. Differential modulation of lipopolysaccharide-induced expression of inflammatory genes in equine monocytes through activation of adenosine A2A receptors.. Vet Immunol Immunopathol 2010 Apr 15;134(3-4):169-77.
    pubmed: 19766323doi: 10.1016/j.vetimm.2009.08.018google scholar: lookup

Citations

This article has been cited 8 times.
  1. Kang H, Lee GKC, Bienzle D, Arroyo LG, Sears W, Lillie BN, Beeler-Marfisi J. Equine alveolar macrophages and monocyte-derived macrophages respond differently to an inflammatory stimulus. PLoS One 2023;18(3):e0282738.
    doi: 10.1371/journal.pone.0282738pubmed: 36920969google scholar: lookup
  2. Basano I, Romolo A, Iamone G, Memoli G, Riccio B, Lavoie JP, Miniscalco B, Bullone M. Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma. Animals (Basel) 2022 Apr 20;12(9).
    doi: 10.3390/ani12091070pubmed: 35565497google scholar: lookup
  3. Di Pietro R, Dubuc V, Manguin E, Giroux-Lafond R, Bédard C, Boivin R, Lavoie JP, Vesper SJ, Leclere M. Characterization of fungal exposure and dectin-1 expression in healthy horses and horses with severe asthma. Am J Vet Res 2022 May 8;83(6).
    doi: 10.2460/ajvr.21.09.0143pubmed: 35524958google scholar: lookup
  4. 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).
    doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
  5. Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W. Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses. Animals (Basel) 2021 Nov 13;11(11).
    doi: 10.3390/ani11113247pubmed: 34827979google scholar: lookup
  6. Kang H, Bienzle D, Lee GKC, Piché É, Viel L, Odemuyiwa SO, Beeler-Marfisi J. Flow cytometric analysis of equine bronchoalveolar lavage fluid cells in horses with and without severe equine asthma. Vet Pathol 2022 Jan;59(1):91-99.
    doi: 10.1177/03009858211042588pubmed: 34521286google scholar: lookup
  7. Woo YD, Jeong D, Chung DH. Development and Functions of Alveolar Macrophages. Mol Cells 2021 May 31;44(5):292-300.
    doi: 10.14348/molcells.2021.0058pubmed: 33972474google scholar: lookup
  8. Lendl L, Wirth C, Merle R, Barton AK. Influence of a Standardized Lunging Exercise Test on BALF Cytology in Horses Suffering from Mild-Moderate Equine Asthma. Animals (Basel) 2025 Aug 19;15(16).
    doi: 10.3390/ani15162428pubmed: 40867756google scholar: lookup
Subscribe to our newsletter
Join 100,129 horse owners like you who receive our email updates on horse health and nutrition.