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Journal of veterinary science2016; 18(1); 17-23; doi: 10.4142/jvs.2017.18.1.17

Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals.

Abstract: Sepsis causes significant mortality in neonatal foals; however, there is little data describing the cellular and molecular pathways of lung inflammation in septic foals. This study was conducted to characterize lung inflammation in septic foals. Lung tissue sections from control (n = 6) and septic (n = 17) foals were compared using histology and immunohistology. Blinded pathologic scoring of hematoxylin and eosin stained samples revealed increased features of lung inflammation such as thickened alveolar septa and sequestered inflammatory cells in septic foals. Septic foal lungs showed increased expression of von Willebrand factor in blood vessels, demonstrating vascular inflammation. Use of MAC387 antibody to detect calprotectin as a reflection of mononuclear cell infiltration revealed a significant increase in their numbers in alveolar septa of lungs from septic foals compared to those from control foals. The mononuclear cells appeared to be mature macrophages and were located in the septal capillaries, suggesting they were pulmonary intravascular macrophages (PIMs). Finally, lungs from septic foals showed increased expression of Toll-like receptor 4 and 9 in mononuclear cells relative to the control. Taken together, this study is the first to show the expression of inflammatory molecules and an increase in PIMs in lungs from foals that died from sepsis.
Publication Date: 2016-06-15 PubMed ID: 27297419PubMed Central: PMC5366298DOI: 10.4142/jvs.2017.18.1.17Google Scholar: Lookup
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  • Journal Article

Summary

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The research article abstract outlines a study that investigates lung inflammation in foals who died from sepsis. The study reveals the presence of increased inflammatory molecules and macrophages in their lungs compared to healthy foals.

Objective of the Study

  • The main objective of the study was to characterize lung inflammation in septic foals and differentiate it from that in healthy foals. Limited prior studies had delved into the molecular and cellular processes related to lung inflammation in septic foals, and this research aimed to fill that gap.

Methodology

  • Six healthy foals and 17 septic foal lungs were selected for the study.
  • Pieces of lung tissues from both sets of foals were analyzed using histology and immunohistology, comparative scientific techniques that study the microscopic anatomy and its variation in diseased conditions.
  • The samples were stained with hematoxylin and eosin, a common technique in histology for the visualization of tissue structure.

Findings of the Study

  • The stained specimens from the septic foals revealed increased features of lung inflammation compared to the healthy ones.
  • Elements of inflammation included thickened alveolar septa (dividing walls in the lungs) and sequestered inflammatory cells.
  • These findings suggested vascular inflammation given the increased expression of Von Willebrand factor, a blood protein that helps clotting, in the blood vessels of the septic foals.
  • Using the MAC387 antibody, which is known to detect calprotectin (a marker of inflammation), scientists observed a significant increase in mononuclear cells in the alveolar septa of septic foals. The presence of mature macrophages showed that these mononuclear cells were pulmonary intravascular macrophages (PIMs).
  • Additionally, expression of Toll-like receptors 4 and 9, integral parts of the immune system, was found to be upregulated in the mononuclear cells of the septic foals’ lungs.

Conclusion

  • This research sheds light on the inflammatory pathways involved in foal lung sepsis, notably the increase in PIMs and upregulation of certain Toll-like receptors.
  • The research is significant for introducing a new dimension of understanding sepsis-associated inflammation in young horses, which ultimately could lead to better management and therapeutic strategies.

Cite This Article

APA
Harrison JM, Quanstrom LM, Robinson AR, Wobeser B, Anderson SL, Singh B. (2016). Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals. J Vet Sci, 18(1), 17-23. https://doi.org/10.4142/jvs.2017.18.1.17

Publication

ISSN: 1976-555X
NlmUniqueID: 100964185
Country: Korea (South)
Language: English
Volume: 18
Issue: 1
Pages: 17-23

Researcher Affiliations

Harrison, Jacqueline M E
  • Department of Veterinary Biomedical Sciences Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Quanstrom, Leah M
  • Department of Veterinary Biomedical Sciences Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Robinson, Alex R
  • Department of Veterinary Biomedical Sciences Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Wobeser, Bruce
  • Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Anderson, Stacy L
  • Department of Veterinary Biomedical Sciences Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Singh, Baljit
  • Department of Veterinary Biomedical Sciences Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.

MeSH Terms

  • Animals
  • Gene Expression
  • Horse Diseases / genetics
  • Horse Diseases / immunology
  • Horse Diseases / microbiology
  • Horses
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / microbiology
  • Inflammation / veterinary
  • Lung / metabolism
  • Macrophages, Alveolar / metabolism
  • Sepsis / genetics
  • Sepsis / immunology
  • Sepsis / microbiology
  • Sepsis / veterinary
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 31 references
  1. Atwal OS. Pulmonary intravascular macrophages (PIMs) and cationised ferritin-induced phagocytosis of platelets: a morphological study.. Comp Haematol Int 1992;2:179–185.
  2. Brewer BD, Koterba AM. Development of a scoring system for the early diagnosis of equine neonatal sepsis.. Equine Vet J 1988 Jan;20(1):18-22.
  3. Charavaryamath C, Janardhan KS, Caldwell S, Singh B. Pulmonary intravascular monocytes/macrophages in a rat model of sepsis.. Anat Rec A Discov Mol Cell Evol Biol 2006 Dec;288(12):1259-71.
    pubmed: 17075848doi: 10.1002/ar.a.20401google scholar: lookup
  4. Cunningham AJ. Acute respiratory distress syndrome--two decades later.. Yale J Biol Med 1991 Jul-Aug;64(4):387-402.
    pmc: PMC2589549pubmed: 1814055
  5. DiStasi MR, Ley K. Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability.. Trends Immunol 2009 Nov;30(11):547-56.
    pmc: PMC2767453pubmed: 19783480doi: 10.1016/j.it.2009.07.012google scholar: lookup
  6. Dunkel B, Dolente B, Boston RC. Acute lung injury/acute respiratory distress syndrome in 15 foals.. Equine Vet J 2005 Sep;37(5):435-40.
    pubmed: 16163946doi: 10.2746/042516405774480094google scholar: lookup
  7. Esmon CT, Xu J, Lupu F. Innate immunity and coagulation.. J Thromb Haemost 2011 Jul;9 Suppl 1(Suppl 1):182-8.
  8. Frevert CW, Warner AE. Respiratory distress resulting from acute lung injury in the veterinary patient.. J Vet Intern Med 1992 May-Jun;6(3):154-65.
  9. Gill SS, Suri SS, Janardhan KS, Caldwell S, Duke T, Singh B. Role of pulmonary intravascular macrophages in endotoxin-induced lung inflammation and mortality in a rat model.. Respir Res 2008 Oct 24;9(1):69.
    pmc: PMC2584635pubmed: 18950499doi: 10.1186/1465-9921-9-69google scholar: lookup
  10. Hall KK, Lyman JA. Updated review of blood culture contamination.. Clin Microbiol Rev 2006 Oct;19(4):788-802.
    pmc: PMC1592696pubmed: 17041144doi: 10.1128/cmr.00062-05google scholar: lookup
  11. Janardhan KS, McIsaac M, Fowlie J, Shrivastav A, Caldwell S, Sharma RK, Singh B. Toll like receptor-4 expression in lipopolysaccharide induced lung inflammation.. Histol Histopathol 2006 Jul;21(7):687-96.
    pubmed: 16598667doi: 10.14670/hh-21.687google scholar: lookup
  12. Johnson L, Montgomery JB, Schneider JP, Townsend HG, Ochs M, Singh B. Morphometric examination of the equine adult and foal lung.. Anat Rec (Hoboken) 2014 Oct;297(10):1950-62.
    pubmed: 25044581doi: 10.1002/ar.22994google scholar: lookup
  13. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation.. Nat Rev Immunol 2013 Mar;13(3):159-75.
    pubmed: 23435331doi: 10.1038/nri3399google scholar: lookup
  14. Lenting PJ, Christophe OD, Denis CV. von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends.. Blood 2015 Mar 26;125(13):2019-28.
    pubmed: 25712991doi: 10.1182/blood-2014-06-528406google scholar: lookup
  15. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses.. Clin Microbiol Rev 2009 Apr;22(2):240-73, Table of Contents.
    pmc: PMC2668232pubmed: 19366914doi: 10.1128/cmr.00046-08google scholar: lookup
  16. Morris DD. Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis.. J Vet Intern Med 1991 May-Jun;5(3):167-81.
  17. Parbhakar OP, Duke T, Townsend HG, Singh B. Depletion of pulmonary intravascular macrophages partially inhibits lipopolysaccharide-induced lung inflammation in horses.. Vet Res 2005 Jul-Aug;36(4):557-69.
    pubmed: 15955281doi: 10.1051/vetres:2005016google scholar: lookup
  18. Raisis AL, Hodgson JL, Hodgson DR. Equine neonatal septicaemia: 24 cases.. Aust Vet J 1996 Apr;73(4):137-40.
  19. Roy MF. Sepsis in adults and foals.. Vet Clin North Am Equine Pract 2004 Apr;20(1):41-61.
    pubmed: 15062458doi: 10.1016/j.cveq.2003.12.005google scholar: lookup
  20. Sanchez LC. Equine neonatal sepsis.. Vet Clin North Am Equine Pract 2005 Aug;21(2):273-93, v.
    pubmed: 16051050doi: 10.1016/j.cveq.2005.04.007google scholar: lookup
  21. Schneberger D, Aharonson-Raz K, Singh B. Pulmonary intravascular macrophages and lung health: what are we missing?. Am J Physiol Lung Cell Mol Physiol 2012 Mar 15;302(6):L498-503.
    pubmed: 22227203doi: 10.1152/ajplung.00322.2011google scholar: lookup
  22. Schneberger D, Caldwell S, Suri SS, Singh B. Expression of toll-like receptor 9 in horse lungs.. Anat Rec (Hoboken) 2009 Jul;292(7):1068-77.
    pubmed: 19548205doi: 10.1002/ar.20927google scholar: lookup
  23. Shrum B, Anantha RV, Xu SX, Donnelly M, Haeryfar SM, McCormick JK, Mele T. A robust scoring system to evaluate sepsis severity in an animal model.. BMC Res Notes 2014 Apr 12;7:233.
    pmc: PMC4022086pubmed: 24725742doi: 10.1186/1756-0500-7-233google scholar: lookup
  24. Singh B, Pearce JW, Gamage LN, Janardhan K, Caldwell S. Depletion of pulmonary intravascular macrophages inhibits acute lung inflammation.. Am J Physiol Lung Cell Mol Physiol 2004 Feb;286(2):L363-72.
    pubmed: 14565942doi: 10.1152/ajplung.00003.2003google scholar: lookup
  25. Taylor S. A review of equine sepsis.. Equine Vet Educ 2015;27:99–109.
  26. Theelen MJ, Wilson WD, Edman JM, Magdesian KG, Kass PH. Temporal trends in prevalence of bacteria isolated from foals with sepsis: 1979-2010.. Equine Vet J 2014 Mar;46(2):169-73.
    pubmed: 23808819doi: 10.1111/evj.12131google scholar: lookup
  27. Wassef A, Janardhan K, Pearce JW, Singh B. Toll-like receptor 4 in normal and inflamed lungs and other organs of pig, dog and cattle.. Histol Histopathol 2004 Oct;19(4):1201-8.
    pubmed: 15375763doi: 10.14670/hh-19.1201google scholar: lookup
  28. Weber EJ, Sanchez LC, Giguère S. Re-evaluation of the sepsis score in equine neonates.. Equine Vet J 2015 May;47(3):275-8.
    pubmed: 24750245doi: 10.1111/evj.12279google scholar: lookup
  29. Wilkins PA, Otto CM, Baumgardner JE, Dunkel B, Bedenice D, Paradis MR, Staffieri F, Syring RS, Slack J, Grasso S, Pranzo EG. Acute lung injury and acute respiratory distress syndromes in veterinary medicine: consensus definitions: The Dorothy Russell Havemeyer Working Group on ALI and ARDS in Veterinary Medicine.. J Vet Emerg Crit Care 2007;17:333–339.
  30. Wilson RF, Sibbald WJ. Acute respiratory failure.. Crit Care Med 1976 Mar-Apr;4(2):79-89.
  31. Winkler GC. Pulmonary intravascular macrophages in domestic animal species: review of structural and functional properties.. Am J Anat 1988 Mar;181(3):217-34.
    pubmed: 3284325doi: 10.1002/aja.1001810302google scholar: lookup

Citations

This article has been cited 4 times.
  1. Sengupta A, Dorn A, Jamshidi M, Schwob M, Hassan W, De Maddalena LL, Hugi A, Stucki AO, Dorn P, Marti TM, Wisser O, Stucki JD, Krebs T, Hobi N, Guenat OT. A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip. Front Pharmacol 2023;14:1114739.
    doi: 10.3389/fphar.2023.1114739pubmed: 36959848google scholar: lookup
  2. Townsend M, Fowler B, Aulakh GK, Singh B. Expression of pentraxin 3 in equine lungs and neutrophils. Can J Vet Res 2023 Jan;87(1):9-16.
    pubmed: 36606044
  3. Bocking T, Johnson L, Singh A, Desai A, Aulakh GK, Singh B. Research article expression of surfactant protein-A and D, and CD9 in lungs of 1 and 30 day old foals. BMC Vet Res 2021 Jul 5;17(1):236.
    doi: 10.1186/s12917-021-02943-5pubmed: 34225699google scholar: lookup
  4. Le NPK, Gerdts V, Singh B. Integrin alpha-v/beta3 expression in equine lungs and jejunum. Can J Vet Res 2020 Oct;84(4):245-251.
    pubmed: 33012972