FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Animals : an open access journal from MDPI2022; 12(9); 1070; doi: 10.3390/ani12091070

Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma.

Abstract: Equine asthma is currently diagnosed by the presence of increased neutrophil (>5%), mast cell (>2%), and/or eosinophil (>1%) differential cell count. Macrophages are normal resident cells within the alveoli. Their presence in BALF is considered normal, but the clinical implication of the presence of activated or fused macrophages (giant multinucleated cells, GMC) is currently overlooked. We aimed to assess the prevalence, cytological determinants, and clinical significance of increased GMC counts in BALF of 34 asthmatic horses compared to 10 controls. Counts were performed on 15 randomly selected high magnification fields per cytospin slide (40×), and expressed as GMC:single macrophage (GMC:M) ratio. Regression models were used for statistical analysis. GMC was frequently observed in both asthmatic and control horses, with an increased prevalence of equine asthma (p = 0.01). GMC:M ratio was significantly higher in severe vs. mild to moderate equine asthmatic and control horses. In asthmatic horses, an increased GMC:M ratio was significantly associated with BALF mastocytosis (p = 0.01), once adjusting for age and the presence and severity of clinical signs of the horses. Tachypnea was the only clinical sign that tended to be positively associated with GMC:M ratio after adjustment (p = 0.08). In conclusion, our data suggest that a relationship might exist between molecular mechanisms regulating GMC formation and mast cell recruitment in the equine lung. The same mechanisms could lead to tachypnea even in the absence of respiratory effort at rest. We suggest including GMC count in the basic cytological assessment of BALF samples to gain more insights into their role in equine asthma.
Get Full Text
Publication Date: 2022-04-20 PubMed ID: 35565497PubMed Central: PMC9103648DOI: 10.3390/ani12091070Google 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 research explores the presence of large multi-nucleated cells (GMC) and their relationship with asthma in horses. The study provides evidence that increased counts of these cells are associated with inflammation due to an increase in mast cells in the lungs, which could be a contributing factor to the development of equine asthma.

Study Design and Purpose

The researchers intended to investigate the prevalence and clinical significance of GMCs in the bronchoalveolar lavage fluid (BALF) obtained from 34 asthmatic horses compared to 10 healthy controls. They hypothesized that increased GMC counts could be overlooked but significant markers in diagnosing equine asthma.

Procedure and Analysis

  • Counts were carried out on high magnification fields of cytospin slides taken from the sampled BALF.
  • The data was presented as a ratio of GMC to single macrophages (GMC:M) and statistical analysis was performed using regression models.

Findings

  • GMCs were found in both asthmatic and control horses but were significantly more prevalent in asthmatic ones.
  • The GMC:M ratio was significantly higher in horses with severe asthma compared to those with moderate or mild asthma and non-asthmatic horses.
  • An increased GMC:M ratio was associated with BALF mastocytosis, a condition characterized by an increased number of mast cells, after adjusting for age and the presence and severity of clinical signs.
  • The only clinical sign that tended to be positively associated with a higher GMC:M ratio was tachypnea (rapid breathing), particularly in the absence of respiratory effort at rest.

Implications

The results indicate a potential link between the molecular processes that regulate the formation of GMCs and the recruitment of mast cells in the lungs of horses. This may be significant, as mast cells play a role in inflammation, which is a central component of asthma. The researchers therefore suggest incorporating GMC count into the basic cytological assessment of BALF samples to yield greater insights into their role in equine asthma.

Cite This Article

APA
Basano I, Romolo A, Iamone G, Memoli G, Riccio B, Lavoie JP, Miniscalco B, Bullone M. (2022). Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma. Animals (Basel), 12(9), 1070. https://doi.org/10.3390/ani12091070

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 12
Issue: 9
PII: 1070

Researcher Affiliations

Basano, Ilaria
  • Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.
Romolo, Alessandra
  • Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.
Iamone, Giulia
  • Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.
Memoli, Giulia
  • Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.
Riccio, Barbara
  • Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.
Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, Canada.
Miniscalco, Barbara
  • Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.
Bullone, Michela
  • Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 40 references
  1. Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
    doi: 10.1111/jvim.13824pmc: PMC4913592pubmed: 26806374google scholar: lookup
  2. Jean D, Vrins A, Beauchamp G, Lavoie JP. Evaluation of variations in bronchoalveolar lavage fluid in horses with recurrent airway obstruction.. Am J Vet Res 2011 Jun;72(6):838-42.
    doi: 10.2460/ajvr.72.6.838pubmed: 21627532google scholar: lookup
  3. Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA. Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile.. Am J Respir Crit Care Med 2001 Oct 15;164(8 Pt 1):1410-3.
    doi: 10.1164/ajrccm.164.8.2012091pubmed: 11704587google scholar: lookup
  4. Klukowska-Rötzler J, Swinburne JE, Drögemüller C, Dolf G, Janda J, Leeb T, Gerber V. The interleukin 4 receptor gene and its role in recurrent airway obstruction in Swiss Warmblood horses.. Anim Genet 2012 Aug;43(4):450-3.
    doi: 10.1111/j.1365-2052.2011.02277.xpubmed: 22497430google scholar: lookup
  5. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
    doi: 10.1111/j.1440-1843.2011.02033.xpubmed: 21824219google scholar: lookup
  6. Jost U, Klukowska-Rötzler J, Dolf G, Swinburne JE, Ramseyer A, Bugno M, Burger D, Blott S, Gerber V. A region on equine chromosome 13 is linked to recurrent airway obstruction in horses.. Equine Vet J 2007 May;39(3):236-41.
    doi: 10.2746/042516407X171110pubmed: 17520975google scholar: lookup
  7. Pirie RS, Collie DD, Dixon PM, McGorum BC. Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 2: Effects of inhaled HDS on control and heaves horses.. Equine Vet J 2002 Jul;34(4):337-42.
    doi: 10.2746/042516402776249074pubmed: 12117104google scholar: lookup
  8. Pirie RS, Collie DD, Dixon PM, McGorum BC. Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma).. Clin Exp Allergy 2003 May;33(5):676-83.
    doi: 10.1046/j.1365-2222.2003.01640.xpubmed: 12752598google scholar: lookup
  9. 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.
    doi: 10.2746/042516401776249732pubmed: 11352355google scholar: lookup
  10. Pirie RS, Dixon PM, McGorum BC. Endotoxin contamination contributes to the pulmonary inflammatory and functional response to Aspergillus fumigatus extract inhalation in heaves horses.. Clin Exp Allergy 2003 Sep;33(9):1289-96.
    doi: 10.1046/j.1365-2745.2003.01651.xpubmed: 12956737google scholar: lookup
  11. Costa LR, Johnson JR, Baur ME, Beadle RE. Temporal clinical exacerbation of summer pasture-associated recurrent airway obstruction and relationship with climate and aeroallergens in horses.. Am J Vet Res 2006 Sep;67(9):1635-42.
    doi: 10.2460/ajvr.67.9.1635pubmed: 16948614google scholar: lookup
  12. Bullone M, Murcia RY, Lavoie JP. Environmental heat and airborne pollen concentration are associated with increased asthma severity in horses.. Equine Vet J 2016 Jul;48(4):479-84.
    doi: 10.1111/evj.12559pubmed: 26708931google scholar: lookup
  13. McGorum BC, Dixon PM, Halliwell RE. Phenotypic analysis of peripheral blood and bronchoalveolar lavage fluid lymphocytes in control and chronic obstructive pulmonary disease affected horses, before and after 'natural (hay and straw) challenges'.. Vet Immunol Immunopathol 1993 Apr;36(3):207-22.
    doi: 10.1016/0165-2427(93)90020-5pubmed: 7685131google scholar: lookup
  14. Schmallenbach KH, Rahman I, Sasse HH, Dixon PM, Halliwell RE, McGorum BC, Crameri R, Miller HR. Studies on pulmonary and systemic Aspergillus fumigatus-specific IgE and IgG antibodies in horses affected with chronic obstructive pulmonary disease (COPD).. Vet Immunol Immunopathol 1998 Dec 11;66(3-4):245-56.
    doi: 10.1016/S0165-2427(98)00202-5pubmed: 9880102google scholar: lookup
  15. Christmann U, Buechner-Maxwell VA, Witonsky SG, Hite RD. Role of lung surfactant in respiratory disease: current knowledge in large animal medicine.. J Vet Intern Med 2009 Mar-Apr;23(2):227-42.
    doi: 10.1111/j.1939-1676.2008.0269.xpubmed: 19192153google scholar: lookup
  16. Gerber V, Robinson NE, Luethi S, Marti E, Wampfler B, Straub R. Airway inflammation and mucus in two age groups of asymptomatic well-performing sport horses.. Equine Vet J 2003 Jul;35(5):491-5.
    doi: 10.2746/042516403775600424pubmed: 12875328google scholar: lookup
  17. Brooks PJ, Glogauer M, McCulloch CA. An Overview of the Derivation and Function of Multinucleated Giant Cells and Their Role in Pathologic Processes.. Am J Pathol 2019 Jun;189(6):1145-1158.
    doi: 10.1016/j.ajpath.2019.02.006pubmed: 30926333google scholar: lookup
  18. Cordeau ME, Joubert P, Dewachi O, Hamid Q, Lavoie JP. IL-4, IL-5 and IFN-gamma mRNA expression in pulmonary lymphocytes in equine heaves.. Vet Immunol Immunopathol 2004 Jan;97(1-2):87-96.
    doi: 10.1016/j.vetimm.2003.08.013pubmed: 14700540google scholar: lookup
  19. Lavoie-Lamoureux A, Moran K, Beauchamp G, Mauel S, Steinbach F, Lefebvre-Lavoie J, Martin JG, Lavoie JP. IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo.. Am J Physiol Lung Cell Mol Physiol 2010 Oct;299(4):L472-82.
    doi: 10.1152/ajplung.00135.2009pubmed: 20639353google scholar: lookup
  20. Moreno JL, Mikhailenko I, Tondravi MM, Keegan AD. IL-4 promotes the formation of multinucleated giant cells from macrophage precursors by a STAT6-dependent, homotypic mechanism: contribution of E-cadherin.. J Leukoc Biol 2007 Dec;82(6):1542-53.
    doi: 10.1189/jlb.0107058pubmed: 17855502google scholar: lookup
  21. Caslin HL, Kiwanuka KN, Haque TT, Taruselli MT, MacKnight HP, Paranjape A, Ryan JJ. Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today.. Front Immunol 2018;9:868.
    doi: 10.3389/fimmu.2018.00868pmc: PMC5932183pubmed: 29755466google scholar: lookup
  22. Hoffman AM. Bronchoalveolar lavage: sampling technique and guidelines for cytologic preparation and interpretation.. Vet Clin North Am Equine Pract 2008 Aug;24(2):423-35, vii-viii.
    doi: 10.1016/j.cveq.2008.04.003pubmed: 18652963google scholar: lookup
  23. Fernandez NJ, Hecker KG, Gilroy CV, Warren AL, Léguillette R. Reliability of 400-cell and 5-field leukocyte differential counts for equine bronchoalveolar lavage fluid.. Vet Clin Pathol 2013 Mar;42(1):92-8.
    doi: 10.1111/vcp.12013pubmed: 23289790google scholar: lookup
  24. Karagianni AE, Lisowski ZM, Hume DA, Scott Pirie R. The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity.. Equine Vet J 2021 Mar;53(2):231-249.
    doi: 10.1111/evj.13341pubmed: 32881079google scholar: lookup
  25. Kern I, Kecelj P, Kosnik M, Mermolja M. Multinucleated giant cells in bronchoalveolar lavage.. Acta Cytol 2003 May-Jun;47(3):426-30.
    doi: 10.1159/000326545pubmed: 12789926google scholar: lookup
  26. Lemaire I, Yang H, Lauzon W, Gendron N. M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes.. J Leukoc Biol 1996 Oct;60(4):509-18.
    doi: 10.1002/jlb.60.4.509pubmed: 8864136google scholar: lookup
  27. 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.2020.105436pmc: PMC7768773pubmed: 32113585google scholar: lookup
  28. Bullone M, Joubert P, Gagné A, Lavoie JP, Hélie P. Bronchoalveolar lavage fluid neutrophilia is associated with the severity of pulmonary lesions during equine asthma exacerbations.. Equine Vet J 2018 Sep;50(5):609-615.
    doi: 10.1111/evj.12806pubmed: 29341228google scholar: lookup
  29. Wenzel SE, Vitari CA, Shende M, Strollo DC, Larkin A, Yousem SA. Asthmatic granulomatosis: a novel disease with asthmatic and granulomatous features.. Am J Respir Crit Care Med 2012 Sep 15;186(6):501-7.
    doi: 10.1164/rccm.201203-0476OCpubmed: 22773731google scholar: lookup
  30. Umezawa H, Naito Y, Ogasawara T, Takeuchi T, Kasamatsu N, Hashizume I. Idiopathic bronchocentric granulomatosis in an asthmatic adolescent.. Respir Med Case Rep 2015;16:134-6.
    doi: 10.1016/j.rmcr.2015.09.010pmc: PMC4681958pubmed: 26744680google scholar: lookup
  31. 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.
    doi: 10.1165/rcmb.2010-0300OCpubmed: 20935189google scholar: lookup
  32. 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: 10.1177/03009858211042588pmc: PMC8679174pubmed: 34521286google scholar: lookup
  33. 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.
    doi: 10.1016/j.molimm.2014.12.005pubmed: 25547716google scholar: lookup
  34. Leclere M, Desnoyers M, Beauchamp G, Lavoie JP. Comparison of four staining methods for detection of mast cells in equine bronchoalveolar lavage fluid.. J Vet Intern Med 2006 Mar-Apr;20(2):377-81.
    doi: 10.1111/j.1939-1676.2006.tb02871.xpubmed: 16594597google scholar: lookup
  35. Trout KL, Holian A. Macrophage fusion caused by particle instillation.. Curr Res Toxicol 2020 Jun 10;1:42-47.
    doi: 10.1016/j.crtox.2020.04.003pmc: PMC7740110pubmed: 33336194google scholar: lookup
  36. McLeod JJ, Baker B, Ryan JJ. Mast cell production and response to IL-4 and IL-13.. Cytokine 2015 Sep;75(1):57-61.
    doi: 10.1016/j.cyto.2015.05.019pmc: PMC4532630pubmed: 26088754google scholar: lookup
  37. Hansen S, Baptiste KE, Fjeldborg J, Horohov DW. A review of the equine age-related changes in the immune system: comparisons between human and equine aging, with focus on lung-specific immune-aging.. Ageing Res Rev 2015 Mar;20:11-23.
    doi: 10.1016/j.arr.2014.12.002pubmed: 25497559google scholar: lookup
  38. Zissel G, Schlaak M, Müller-Quernheim J. Age-related decrease in accessory cell function of human alveolar macrophages.. J Investig Med 1999 Jan;47(1):51-6.
    pubmed: 10071481
  39. Mohan SV, Liao YJ, Kim JW, Goronzy JJ, Weyand CM. Giant cell arteritis: immune and vascular aging as disease risk factors.. Arthritis Res Ther 2011 Aug 2;13(4):231.
    doi: 10.1186/ar3358pmc: PMC3239337pubmed: 21861860google scholar: lookup
  40. Couëtil LL, Ward MP. Analysis of risk factors for recurrent airway obstruction in North American horses: 1,444 cases (1990-1999).. J Am Vet Med Assoc 2003 Dec 1;223(11):1645-50.
    doi: 10.2460/javma.2003.223.1645pubmed: 14664454google scholar: lookup

Citations

This article has been cited 4 times.
  1. Akula S, Riihimäki M, Waern I, Åbrink M, Raine A, Hellman L, Wernersson S. Quantitative Transcriptome Analysis of Purified Equine Mast Cells Identifies a Dominant Mucosal Mast Cell Population with Possible Inflammatory Functions in Airways of Asthmatic Horses. Int J Mol Sci 2022 Nov 12;23(22).
    doi: 10.3390/ijms232213976pubmed: 36430453google scholar: lookup
  2. Dély S, Gerber V, Peters LM, Sage SE. Association between equine asthma and fungal elements in the tracheal wash: An environment-matched case-control study. PLoS One 2024;19(9):e0309835.
    doi: 10.1371/journal.pone.0309835pubmed: 39240830google scholar: lookup
  3. Mazan MR, Deveney EF. A cross-sectional observational study of birefringent particulates in bronchoalveolar lavage cytology in horses with equine asthma from the West v East coasts of the USA. PLoS One 2024;19(4):e0297181.
    doi: 10.1371/journal.pone.0297181pubmed: 38573986google scholar: lookup
  4. Stucchi L, Lo Feudo CM, Ferrucci F. Equine Respiratory Medicine and Cardiology. Animals (Basel) 2023 Sep 18;13(18).
    doi: 10.3390/ani13182952pubmed: 37760352google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.