FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Equine Vet J / Comparative transcriptome analysis of equine alveolar macrop...
Equine veterinary journal2016; 49(3); 375-382; doi: 10.1111/evj.12584

Comparative transcriptome analysis of equine alveolar macrophages.

Abstract: Alveolar macrophages (AMs) are the first line of defence against pathogens in the lungs of all mammalian species and thus may constitute appropriate therapeutic target cells in the treatment and prevention of opportunistic airway infections. Therefore, acquiring a better understanding of equine macrophage biology is of paramount importance in addressing this issue in relation to the horse. Objective: To compare the transcriptome of equine AMs with that of equine peritoneal macrophages (PMs) and to investigate the effect of lipopolysaccharide (LPS) on equine AM. Methods: Gene expression study of equine AMs. Methods: Cells from both bronchoalveolar and peritoneal lavage fluid were isolated from systemically healthy horses that had been submitted to euthanasia. Cells were cryopreserved. RNA was extracted and comparative microarray analyses were performed in AMs and PMs, and in AMs treated and untreated with LPS. Comparisons with published data derived from human AM studies were made, with particular focus on LPS-induced inflammatory status. Results: The comparison between AMs and PMs revealed the differential basal expression of 451 genes. Gene expression analysis revealed an alternative (M2) macrophage polarisation profile in AMs and a hybrid macrophage activation profile in PMs, a phenomenon potentially attributable to a degree of induced endotoxin tolerance. The gene expression profile of equine AMs following LPS stimulation revealed significant changes in the expression of 240 genes, including well-known upregulated inflammatory genes. This LPS-induced gene expression profile of equine AMs more closely resembles that of human rather than murine macrophages. Conclusions: This study improves current understanding of equine macrophage biology. These data suggest that the horse may represent a suitable animal model for the study of human macrophage-associated lung inflammation and data derived from human macrophage studies may have significant relevance to the horse.
© 2016 The Authors Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Get Full Text
Publication Date: 2016-07-09 PubMed ID: 27096353PubMed Central: PMC5412682DOI: 10.1111/evj.12584Google 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.

This study explored the genetic characteristics and immune activities of specific cells, known as alveolar macrophages, found in horse lungs. Comparisons were made between these cells and similar ones found in the abdominal cavity, and changes were examined after exposure to a bacterial component. The research provides new insights on the immune responses of horses and suggests they might be useful models for studying human lung inflammation.

Research Aims and Methods

  • The aim of the study was to better understand the biology of equine (horse) macrophages, specifically a type called alveolar macrophages (AMs) found in the lungs. These cells play a crucial role in initiating the immune response to lung infections. The researchers wanted to compare these cells with a different kind of macrophage that are found in the peritoneum (the cavity that contains the abdominal organs), known as peritoneal macrophages (PMs).
  • To do this, they isolated these different types of cells from the lungs and peritoneum of healthy horses. They then used laboratory techniques to freeze these cells and extract their RNA, the molecule that carries genetic information.
  • They then used microarray analysis, a laboratory technique that allows the simultaneous measurement of the expression of thousands of genes, to compare the gene activity in the different types of cells.

Results and Findings

  • The researchers found significant differences in gene expression between AMs and PMs, with 451 genes exhibiting different activity between the cell types. This showed that these cells, despite both being types of macrophages, had distinct gene activity patterns and potentially different immune functions.
  • The analysis suggested that AMs were predominantly characterized by an alternative macrophage activation profile, or M2 profile. M2 macrophages play a role in wound healing and the resolution of inflammation. In contrast, PMs demonstrated a hybrid activation profile, involving both M1 (inflammatory) and M2 (anti-inflammatory) macrophages, potentially due to endotoxin tolerance.
  • Upon stimulating AMs with lipopolysaccharide (LPS, a component of certain types of bacteria that can trigger an immune response), 240 genes showed significant changes in their expression. This includes an increased expression of genes linked to inflammation, therefore, suggesting the horse’s immune response to LPS.

Significance and Conclusions

  • The results of this work deepen the understanding of equine macrophage biology, revealing important differences in their immune functions based on their location and also how they respond to bacterial infection.
  • Interestingly, the gene activity pattern seen in equine AMs stimulated with LPS was found to be more similar to that seen in human macrophages rather than in mice, which are commonly used in laboratory studies.
  • This finding, therefore, suggests that horses could represent a useful model for studying lung inflammation in humans and consequently, help to improve treatments and prevention strategies for lung diseases.

Cite This Article

APA
Karagianni AE, Kapetanovic R, Summers KM, McGorum BC, Hume DA, Pirie RS. (2016). Comparative transcriptome analysis of equine alveolar macrophages. Equine Vet J, 49(3), 375-382. https://doi.org/10.1111/evj.12584

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 49
Issue: 3
Pages: 375-382

Researcher Affiliations

Karagianni, A E
  • Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
Kapetanovic, R
  • Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
Summers, K M
  • Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
McGorum, B C
  • Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
Hume, D A
  • Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
Pirie, R S
  • Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.

MeSH Terms

  • Animals
  • Cells, Cultured
  • Gene Expression Regulation / physiology
  • Horses
  • Lipopolysaccharides / pharmacology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism
  • Macrophages, Peritoneal / physiology
  • Transcriptome / physiology

Grant Funding

  • BBS/E/D/20211552 / Biotechnology and Biological Sciences Research Council

References

This article includes 34 references
  1. Aggarwal NR, King LS, D'Alessio FR. Diverse macrophage populations mediate acute lung inflammation and resolution.. Am. J. Physiol. Lung Cell. Mol. Physiol. 2014 306, L709‐L725.
    pmc: PMC3989724pubmed: 24508730
  2. Hussell T, Bell TJ. Alveolar macrophages: plasticity in a tissue‐specific context.. Nat. Rev. Immunol. 2014 14, 81‐93.
    pubmed: 24445666
  3. Lavin Y, Winter D, Blecher‐Gonen R, David E, Keren‐Shaul H, Merad M, Jung S, Amit I. Tissue‐resident macrophage enhancer landscapes are shaped by the local microenvironment.. Cell 2014 159, 1312‐1326.
    pmc: PMC4437213pubmed: 25480296
  4. 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 155, 219‐228.
    pmc: PMC3795452pubmed: 23978307
  5. Laan T, Bull S, Pirie S, 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 66, 1584‐1589.
    pubmed: 16261833
  6. Schroder K, Irvine KM, Taylor MS, Bokil NJ, Cao K‐AL, Masterman KA, Labzin LI, Semple CA, Kapetanovic R, Fairbairn L, Akalin A, Faulkner GJ, Baillie JK, Gongora M, Daub CO, Kawaji H, McLachlan GJ, Goldman N, Grimmond SM, Carninci P, Suzuki H, Hayashizaki Y, Lenhard B, Hume DA, Sweet MJ. Conservation and divergence in Toll‐like receptor 4‐regulated gene expression in primary human versus mouse macrophages.. Proc. Natl. Acad. Sci. U.S.A. 2012 109, E944‐E953.
    pmc: PMC3341041pubmed: 22451944
  7. Junhee S, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Weihong X, Richards DR, McDonald‐Smith GP, Hong G, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Mine JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB. Genomic responses in mouse models poorly mimic human inflammatory diseases.. Proc. Natl. Acad. Sci. U.S.A. 2013 110, 3507‐3512.
    pmc: PMC3587220pubmed: 23401516
  8. Hughes KJ, Malikides N, Hodgson DR, Hodgson JL. Comparison of tracheal aspirates and bronchoalveolar lavage in racehorses 1. Evaluation of cytological stains and the percentage of mast cells and eosinophils.. Aust. Vet. J. 2003 81, 681‐684.
    pubmed: 15086109
  9. Richard EA, Fortier GD, Lekeux PM, Van Erck E. Laboratory findings in respiratory fluids of the poorly‐performing horse.. Vet. J. 2010 185, 115‐122.
    pubmed: 19481964
  10. Koblinger K, Nicol J, McDonald K, Wasko A, Logie N, Weiss M, Léguillette R. Endoscopic assessment of airway inflammation in horses.. J. Vet. Intern. Med. 2011 25, 1118‐1126.
    pubmed: 21985142
  11. Irizarry RA, Hobbs B, Collin F, Beazer‐Barclay YD, Antonellis KJ, Scherf U, Speed TP. Exploration, normalization, and summaries of high density oligonucleotide array probe level data.. Biostatistics 2003 4, 249‐264.
    pubmed: 12925520
  12. Reynier F, de Vos AF, Hoogerwerf JI, Bresser P, van der Zee JS, Paye M, Pachot A, Mougin B, van der Poll T. Gene expression profiles in alveolar macrophages induced by lipopolysaccharide in humans.. Mol. Med. 2012 18, 1303‐1311.
    pmc: PMC3521791pubmed: 22952057
  13. Freeman TC, Goldovsky L, Brosch M, Van Dongen S, Maziere P, Grocock RJ, Freilich S, Thornton J, Enright AJ. Construction, visualisation, and clustering of transcription networks from microarray expression data.. PLoS Comput. Biol. 2007 3, 2032‐2042.
    pmc: PMC2041979pubmed: 17967053
  14. Joshi VD, Kalvakolanu DV, Cross AS. Simultaneous activation of apoptosis and inflammation in pathogenesis of septic shock: a hypothesis.. FEBS Lett. 2003 555, 180‐184.
    pubmed: 14644412
  15. Kapetanovic R, Fairbairn L, Beraldi D, Sester DP, Archibald AL, Tuggle CK, Hume DA. Pig bone marrow‐derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide.. J. Immunol. 2012 188, 3382‐3394.
    pubmed: 22393154
  16. Silva NM, Rodrigues CV, Santoro MM, Reis LFL, Alvarez‐Leite JI, Gazzinelli RT. Expression of indoleamine 2,3‐dioxygenase, tryptophan degradation, and kynurenine formation during in vivo infection with Toxoplasma gondii: induction by endogenous gamma interferon and requirement of interferon regulatory factor 1.. Infect. Immun. 2002 70, 859‐868.
    pmc: PMC127654pubmed: 11796621
  17. Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism.. Nat. Rev. Immunol. 2004 4, 762‐774.
    pubmed: 15459668
  18. Akagawa KS, Komuro I, Kanazawa H, Yamazaki T, Mochida K, Kishi F. Functional heterogeneity of colony‐stimulating factor‐induced human monocyte‐derived macrophages.. Respirology 2006 11, Suppl, 32‐36.
    pubmed: 16423268
  19. Suzuki T, Maranda B, Sakagami T, Catellier P, Couture CY, Carey BC, Chalk C, Trapnell BC. Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations.. Eur. Respir. J. 2011 37, 201‐204.
    pubmed: 21205713
  20. PrabhuDas M, Bowdish D, Drickamer K, Febbraio M, Herz J, Kobzik L, Krieger M, Loike J, Means TK, Moestrup SK, Post S, Sawamura T, Silverstein S, Wang XY, El Khoury J. Standardizing scavenger receptor nomenclature.. J. Immunol. 2014 192, 1997‐2006.
    pmc: PMC4238968pubmed: 24563502
  21. Kapetanovic R, Fairbairn L, Downing A, Beraldi D, Sester DP, Freeman TC, Tuggle CK, Archibald AL, Hume DA. The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide.. BMC Genom. 2013 14, 581‐596.
    pmc: PMC3766131pubmed: 23984833
  22. Freeman TC, Ivens A, Baillie JK, Beraldi D, Barnett MW, Dorward D, Downing A, Fairbairn L, Kapetanovic R, Raza S, Tomoiu A, Alberio R, Wu C, Su AI, Summers KM, Tuggle CK, Archibald AL, Hume DA. A gene expression atlas of the domestic pig.. BMC Biol. 2012 10, 90.
    pmc: PMC3814290pubmed: 23153189
  23. Lambrecht BN. Alveolar macrophage in the driver's seat.. Immunity 2006 24, 366‐368.
    pubmed: 16618595
  24. Jones C, Williams T, Walker K, Dickinson H, Sakkal S, Rumballe B, Little M, Jenkin G, Ricardo S. M2 macrophage polarisation is associated with alveolar formation during postnatal lung development.. Respir. Res. 2013 14, 41.
    pmc: PMC3626876pubmed: 23560845
  25. O'Carroll C, Fagan A, Shanahan F, Carmody RJ. Identification of a unique hybrid macrophage‐polarization state following recovery from lipopolysaccharide tolerance.. J. Immunol. 2014 192, 427‐436.
    pubmed: 24337373
  26. Martin BJ. Inhibiting vasculogenesis after radiation: a new paradigm to improve local control by radiotherapy.. Semin. Radiat. Oncol. 2013 23, 281‐287.
    pmc: PMC3768004pubmed: 24012342
  27. Roda JM, Sumner LA, Evans R, Phillips GS, Marsh CB, Eubank TD. Hypoxia‐inducible factor‐2α regulates GM‐CSF‐derived soluble vascular endothelial growth factor receptor 1 production from macrophages and inhibits tumor growth and angiogenesis.. J. Immunol. 2011 187, 1970‐1976.
    pmc: PMC3150377pubmed: 21765015
  28. Waldschmidt I, Pirottin D, Art T, Audigie F, Bureau F, Tosi I, El Abbas S, Farnir F, Richard E, Dupuis MC. Experimental model of equine alveolar macrophage stimulation with TLR ligands.. Vet. Immunol. Immunopathol. 2013 155, 30‐37.
    pubmed: 23815824
  29. Liu Y, Song M, Che TM, Bravo D, Pettigrew JE. Anti‐inflammatory effects of several plant extracts on porcine alveolar macrophages in vitro.. J. Anim. Sci. 2012 90, 2774‐2783.
    pubmed: 22328722
  30. Figueiredo MD, Vandenplas ML, Hurley DJ, Moore JN. Differential induction of MyD88‐and TRIF‐dependent pathways in equine monocytes by Toll‐like receptor agonists.. Vet. Immunol. Immunopathol. 2009 127, 125‐134.
    pubmed: 19019456
  31. Spence S, Fitzsimons A, Boyd CR, Kessler J, Fitzgerald D, Elliott J, Gabhann JN, Smith S, Sica A, Hams E, Saunders SP, Jefferies CA, Fallon PG, McAuley DF, Kissenpfennig A, Johnston JA. Suppressors of cytokine signaling 2 and 3 diametrically control macrophage polarization.. Immunity 2013 38, 66‐78.
    pubmed: 23177319
  32. Schneemann M, Schoedon G, Hofer S, Blau N, Guerrero L, Guerrero L, Schaffner A. Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes.. J. Infect. Dis. 1993 167, 1358‐1363.
    pubmed: 7684756
  33. Heller MC, Drew CP, Jackson KA, Griffey S, Watson JL. A potential role for indoleamine 2,3‐dioxygenase (IDO) in Rhodococcus equi infection.. Vet. Immunol. Immunopathol. 2010 138, 174‐182.
    pubmed: 20739070
  34. Fairbairn L, Kapetanovic R, Sester DP, Hume DA. The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease.. J. Leukoc. Biol. 2011 89, 855‐871.
    pubmed: 21233410

Citations

This article has been cited 12 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. Sage SE, Nicholson P, Peters LM, Leeb T, Jagannathan V, Gerber V. Single-cell gene expression analysis of cryopreserved equine bronchoalveolar cells. Front Immunol 2022;13:929922.
    doi: 10.3389/fimmu.2022.929922pubmed: 36105804google scholar: lookup
  3. 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
  4. Finno CJ. Science-in-brief: Genomic and transcriptomic approaches to the investigation of equine diseases. Equine Vet J 2022 Mar;54(2):444-448.
    doi: 10.1111/evj.13549pubmed: 35133024google scholar: lookup
  5. Menarim BC, El-Sheikh Ali H, Loux SC, Scoggin KE, Kalbfleisch TS, MacLeod JN, Dahlgren LA. Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis. Front Immunol 2021;12:734322.
    doi: 10.3389/fimmu.2021.734322pubmed: 34956173google scholar: lookup
  6. 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
  7. Menarim BC, MacLeod JN, Dahlgren LA. Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair. World J Stem Cells 2021 Jul 26;13(7):825-840.
    doi: 10.4252/wjsc.v13.i7.825pubmed: 34367479google scholar: lookup
  8. 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.
    doi: 10.1038/s41598-021-93839-9pubmed: 34253818google scholar: lookup
  9. Bush SJ, McCulloch MEB, Lisowski ZM, Muriuki C, Clark EL, Young R, Pridans C, Prendergast JGD, Summers KM, Hume DA. Species-Specificity of Transcriptional Regulation and the Response to Lipopolysaccharide in Mammalian Macrophages. Front Cell Dev Biol 2020;8:661.
    doi: 10.3389/fcell.2020.00661pubmed: 32793601google scholar: lookup
  10. Wilson ME, McCandless EE, Olszewski MA, Robinson NE. Alveolar macrophage phenotypes in severe equine asthma. Vet J 2020 Feb;256:105436.
    doi: 10.1016/j.tvjl.2020.105436pubmed: 32113585google scholar: lookup
  11. Liu H, Feye KM, Nguyen YT, Rakhshandeh A, Loving CL, Dekkers JCM, Gabler NK, Tuggle CK. Acute systemic inflammatory response to lipopolysaccharide stimulation in pigs divergently selected for residual feed intake. BMC Genomics 2019 Oct 11;20(1):728.
    doi: 10.1186/s12864-019-6127-xpubmed: 31610780google scholar: lookup
  12. Zucca E, Corsini E, Galbiati V, Lange-Consiglio A, Ferrucci F. Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation. Stem Cell Res Ther 2016 Sep 20;7(1):137.
    doi: 10.1186/s13287-016-0398-9pubmed: 27651133google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.