Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
권호 표지
DOI QR코드

DOI QR Code

Histopathological evaluation of the lungs in experimental autoimmune encephalomyelitis

  • Sungmoo Hong (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Jeongtae Kim (Department of Anatomy, Kosin University College of Medicine) ;
  • Kyungsook Jung (Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Meejung Ahn (Department of Animal Science, College of Life Science, Sangji University) ;
  • Changjong Moon (Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University) ;
  • Yoshihiro Nomura (Scleroprotein and Leather Research Institute, Faculty of Agriculture, Tokyo University of Agriculture and Technology) ;
  • Hiroshi Matsuda (Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology) ;
  • Akane Tanaka (Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology) ;
  • Hyohoon Jeong (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Taekyun Shin (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
  • Received : 2023.12.01
  • Accepted : 2024.03.07
  • Published : 2024.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

Importance: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. Objective: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. Methods: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. Results: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. Conclusions and Relevance: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

Keywords

Acknowledgement

This research was supported by the 2024 scientific promotion program funded by Jeju National University. The funders had no role in the design, analysis, write-up or decision to submit for publication.

References

  1. Faissner S, Plemel JR, Gold R, Yong VW. Progressive multiple sclerosis: from pathophysiology to therapeutic strategies. Nat Rev Drug Discov. 2019;18(12):905-922.
  2. Doshi A, Chataway J. Multiple sclerosis, a treatable disease. Clin Med (Lond). 2017;17(6):530-536.
  3. Westerdahl E, Gunnarsson M, Wittrin A, Nilsagard Y. Pulmonary function and respiratory muscle strength in patients with multiple sclerosis. Mult Scler Int. 2021;2021:5532776.
  4. Shin T, Kojima T, Tanuma N, Ishihara Y, Matsumoto Y. The subarachnoid space as a site for precursor T cell proliferation and effector T cell selection in experimental autoimmune encephalomyelitis. J Neuroimmunol. 1995;56(2):171-178.
  5. Kanayama M, Danzaki K, He YW, Shinohara ML. Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis. Int Immunol. 2016;28(9):463-469.
  6. Pyka-Fosciak G, Zemla J, Lekki J, Wojcik B, Lis GJ, Litwin JA, et al. Biomechanical changes in the liver tissue induced by a mouse model of multiple sclerosis (EAE) and the effect of anti-VLA-4 mAb treatment. Arch Biochem Biophys. 2022;728:109356.
  7. Shin T, Ahn M, Matsumoto Y. Mechanism of experimental autoimmune encephalomyelitis in Lewis rats: recent insights from macrophages. Anat Cell Biol. 2012;45(3):141-148.
  8. Glenn JD, Liu C, Whartenby KA. Frontline science: induction of experimental autoimmune encephalomyelitis mobilizes Th17-promoting myeloid derived suppressor cells to the lung. J Leukoc Biol. 2019;105(5):829-841.
  9. Jakovac H, Grubic Kezele T, Sucurovic S, Mulac-Jericevic B, Radosevic-Stasic B. Osteopontin-metallothionein I/II interactions in experimental autoimmune encephalomyelitis. Neuroscience. 2017;350:133-145.
  10. Mangano K, Petralia MC, Bella R, Pennisi M, Munoz-Valle JF, Hernandez-Bello J, et al. Transcriptional upregulation of galectin-3 in multiple sclerosis. Immunol Res. 2023;71(6):950-958.
  11. Coulis G, Jaime D, Guerrero-Juarez C, Kastenschmidt JM, Farahat PK, Nguyen Q, et al. Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis. Sci Adv. 2023;9(27):eadd9984.
  12. Clemente N, Comi C, Raineri D, Cappellano G, Vecchio D, Orilieri E, et al. Role of anti-osteopontin antibodies in multiple sclerosis and experimental autoimmune encephalomyelitis. Front Immunol. 2017;8:321.
  13. Kim MD, Cho HJ, Shin T. Expression of osteopontin and its ligand, CD44, in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis. J Neuroimmunol. 2004;151(1-2):78-84.
  14. Someya H, Ito M, Nishio Y, Sato T, Harimoto K, Takeuchi M. Osteopontin-induced vascular hyperpermeability through tight junction disruption in diabetic retina. Exp Eye Res. 2022;220:109094.
  15. Wang J, Li X, Wang Y, Li Y, Shi F, Diao H. Osteopontin aggravates acute lung injury in influenza virus infection by promoting macrophages necroptosis. Cell Death Dis. 2022;8(1):97.
  16. Barkas GI, Kotsiou OS. The role of osteopontin in respiratory health and disease. J Pers Med. 2023;13(8):1259.
  17. Cooper DN. Galectinomics: finding themes in complexity. Biochim Biophys Acta. 2002;1572(2-3):209-231.
  18. Bouffette S, Botez I, De Ceuninck F. Targeting galectin-3 in inflammatory and fibrotic diseases. Trends Pharmacol Sci. 2023;44(8):519-531.
  19. Nishi Y, Sano H, Kawashima T, Okada T, Kuroda T, Kikkawa K, et al. Role of galectin-3 in human pulmonary fibrosis. Allergol Int. 2007;56(1):57-65.
  20. MacKinnon AC, Farnworth SL, Hodkinson PS, Henderson NC, Atkinson KM, Leffler H, et al. Regulation of alternative macrophage activation by galectin-3. J Immunol. 2008;180(4):2650-2658.
  21. Farnworth SL, Henderson NC, Mackinnon AC, Atkinson KM, Wilkinson T, Dhaliwal K, et al. Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function. Am J Pathol. 2008;172(2):395-405.
  22. Sano H, Hsu DK, Yu L, Apgar JR, Kuwabara I, Yamanaka T, et al. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J Immunol. 2000;165(4):2156-2164.
  23. Humphries DC, Mills R, Boz C, McHugh BJ, Hirani N, Rossi AG, et al. Galectin-3 inhibitor GB0139 protects against acute lung injury by inhibiting neutrophil recruitment and activation. Front Pharmacol. 2022;13:949264.
  24. Weerasinghe-Mudiyanselage PDE, Kang S, Kim JS, Kim JC, Kim SH, Wang H, et al. Transcriptome profiling in the hippocampi of mice with experimental autoimmune encephalomyelitis. Int J Mol Sci. 2022;23(23):14829.
  25. Hong S, Weerasinghe-Mudiyanselage PDE, Kang S, Moon C, Shin T. Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis. Anim Cells Syst. 2023;27(1):219-233.
  26. Park C, Kim J, Ahn M, Choi Y, Shin T. Glycan changes in the olfactory mucosa of rats with experimental autoimmune encephalomyelitis. Brain Res. 2020;1732:146649.
  27. Chen Y, Yu Q, Xu CB. A convenient method for quantifying collagen fibers in atherosclerotic lesions by ImageJ software. Int J Clin Exp Med. 2017;10(10):14904-14910.
  28. Choi Y, Oh H, Ahn M, Kang T, Chun J, Shin T, et al. Immunohistochemical analysis of periostin in the hearts of Lewis rats with experimental autoimmune myocarditis. J Vet Med Sci. 2020;82(10):1545-1550.
  29. Jahan-Abad AJ, Karima S, Shateri S, Baram SM, Rajaei S, Morteza-Zadeh P, et al. Serum pro-inflammatory and anti-inflammatory cytokines and the pathogenesis of experimental autoimmune encephalomyelitis. Neuropathology. 2020;40(1):84-92.
  30. Sanchez-Lopez AL, Ortiz GG, Pacheco-Moises FP, Mireles-Ramirez MA, Bitzer-Quintero OK, Delgado-Lara DLC, et al. Efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing remitting multiple sclerosis. Arch Med Res. 2018;49(6):391-398.
  31. Tzelepis GE, McCool FD. Respiratory dysfunction in multiple sclerosis. Respir Med. 2015;109(6):671-679.
  32. Standal T, Borset M, Sundan A. Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol. 2004;26(3):179-184.
  33. Jafarinia M, Sadeghi E, Alsahebfosoul F, Etemadifar M, Jahanbani-Ardakani H. Evaluation of plasma osteopontin level in relapsing-remitting multiple sclerosis patients compared to healthy subjects in Isfahan Province. Int J Neurosci. 2020;130(5):493-498.
  34. Pang X, Zhang J, He X, Gu Y, Qian BZ, Xie R, et al. SPP1 promotes enzalutamide resistance and epithelial-mesenchymal-transition activation in castration-resistant prostate cancer via PI3K/AKT and ERK1/2 pathways. Oxid Med Cell Longev. 2021;2021:5806602.
  35. Behera R, Kumar V, Lohite K, Karnik S, Kundu GC. Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis. 2010;31(2):192-200.
  36. Yang HW, Park JH, Jo MS, Shin JM, Kim DW, Park IH. Eosinophil-derived osteopontin induces the expression of pro-inflammatory mediators and stimulates extracellular matrix production in nasal fibroblasts: the role of osteopontin in eosinophilic chronic rhinosinusitis. Front Immunol. 2022;13:777928.
  37. Khamissi FZ, Ning L, Kefaloyianni E, Dun H, Arthanarisami A, Keller A, et al. Identification of kidney injury released circulating osteopontin as causal agent of respiratory failure. Sci Adv. 2022;8(8):eabm5900.
  38. Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009;230(1):160-171.
  39. Gittens BR, Bodkin JV, Nourshargh S, Perretti M, Cooper D. Galectin-3: a positive regulator of leukocyte recruitment in the inflamed microcirculation. J Immunol. 2017;198(11):4458-4469.
  40. Slack RJ, Mills R, Mackinnon AC. The therapeutic potential of galectin-3 inhibition in fibrotic disease. Int J Biochem Cell Biol. 2021;130:105881.
  41. Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, Denhardt DT, et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science. 2001;294(5547):1731-1735.
  42. Jiang HR, Al Rasebi Z, Mensah-Brown E, Shahin A, Xu D, Goodyear CS, et al. Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. J Immunol. 2009;182(2):1167-1173.