• 1. McGorum BC, Dixon P, Halliwell R. Responses of horses affected with chronic obstructive pulmonary disease to inhalation challenges with mold antigens. Equine Vet J 1993; 25: 261267.

    • Search Google Scholar
    • Export Citation
  • 2. Thomson JR, McPherson E. Effects of environmental control on pulmonary function of horses affected with chronic obstructive pulmonary disease. Equine Vet J 1984; 16: 3538.

    • Search Google Scholar
    • Export Citation
  • 3. Couëtil LL, Cardwell JM, Gerber V, et al. Inflammatory airway disease of horses—revised consensus statement. J Vet Intern Med 2016; 30: 503515.

    • Search Google Scholar
    • Export Citation
  • 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; 66: 97105.

    • Search Google Scholar
    • Export Citation
  • 5. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses. Respirology 2011; 16: 10271046.

  • 6. Robinson NE. International workshop on equine chronic airway disease. Michigan State University 16–18 June 2000. Equine Vet J 2001; 33: 519.

    • Search Google Scholar
    • Export Citation
  • 7. Couëtil L, Hawkins J. The coughing horse. In: Couëtil L, Hawkins J, eds. Respiratory diseases of the horse: a problem-oriented approach to diagnosis & management. London: Manson Publishing Ltd, 2013; 77102.

    • Search Google Scholar
    • Export Citation
  • 8. Gabison EE, Hoang-Xuan T, Mauviel A, et al. EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie 2005; 87: 361368.

    • Search Google Scholar
    • Export Citation
  • 9. Grass GD, Toole BP. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity. Biosci Rep 2015; 36: e00283.

    • Search Google Scholar
    • Export Citation
  • 10. Odajima N, Betsuyaku T, Nasuhara Y, et al. Extracellular matrix metalloproteinase inducer in interstitial pneumonias. Hum Pathol 2006; 37: 10581065.

    • Search Google Scholar
    • Export Citation
  • 11. Zhou J, Zhu P, Jiang JL, et al. Involvement of CD147 in over-expression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1. BMC Cell Biol 2005; 6: 25.

    • Search Google Scholar
    • Export Citation
  • 12. Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted. Physiol Rev 2007; 87: 6998.

    • Search Google Scholar
    • Export Citation
  • 13. Xiong L, Edwards CK III, Zhou L. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature. Int J Mol Sci 2014; 15: 1741117441.

    • Search Google Scholar
    • Export Citation
  • 14. Betsuyaku T, Tanino M, Nagai K, et al. Extracellular matrix metalloproteinase inducer is increased in smokers' bronchoalveolar lavage fluid. Am J Respir Crit Care Med 2003; 168: 222227.

    • Search Google Scholar
    • Export Citation
  • 15. Gwinn WM, Damsker JM, Falahati R, et al. Novel approach to inhibit asthma-mediated lung inflammation using anti-CD147 intervention. J Immunol 2006; 177: 48704879.

    • Search Google Scholar
    • Export Citation
  • 16. Jouneau S, Khorasani N, De Souza P, et al. EMMPRIN (CD147) regulation of MMP-9 in bronchial epithelial cells in COPD. Respirology 2011; 16: 705712.

    • Search Google Scholar
    • Export Citation
  • 17. Han Z. Junxu, Zhong N. Expression of matrix metalloproteinases MMP-9 within the airways in asthma. Respir Med 2003; 97: 563567.

  • 18. Koivunen AL, Maisi P, Konttinen YT, et al. Gelatinolytic activity in tracheal aspirates of horses with chronic obstructive pulmonary disease. Acta Vet Scand 1997; 38: 1727.

    • Search Google Scholar
    • Export Citation
  • 19. Raulo SM, Maisi P. Gelatinolytic activity in tracheal epithelial lining fluid and in blood from horses with chronic obstructive pulmonary disease. Am J Vet Res 1998; 59: 818823.

    • Search Google Scholar
    • Export Citation
  • 20. Raulo SM, Sorsa T, Tervahartiala T, et al. MMP-9 as a marker of inflammation in tracheal epithelial lining fluid (TELF) and in bronchoalveolar fluid (BALF) of COPD horses. Equine Vet J 2001; 33: 128136.

    • Search Google Scholar
    • Export Citation
  • 21. Koho NM, Hyyppä S, Pösö AR. Monocarboxylate transporters (MCT) as lactate carriers in equine muscle and red blood cells. Equine Vet J Suppl 2006; 36: 354358.

    • Search Google Scholar
    • Export Citation
  • 22. Koho NM, Väihkönen LK, Pösö AR. Lactate transport in red blood cells by monocarboxylate transporters. Equine Vet J Suppl 2002; 34: 555559.

    • Search Google Scholar
    • Export Citation
  • 23. Couëtil L, Hawkins J. Diagnostic tests and therapeutic procedures. In: Couëtil L, Hawkins J, eds. Respiratory diseases of the horse: a problem-oriented approach to diagnosis & management. London: Manson Publishing Ltd, 2013; 4776.

    • Search Google Scholar
    • Export Citation
  • 24. McGorum BC, Dixon PM, Halliwell RE, et al. Evaluation of urea and albumen as endogenous markers of dilution of equine bronchoalveolar lavage fluid. Res Vet Sci 1993; 55: 5256.

    • Search Google Scholar
    • Export Citation
  • 25. Hasaneen NA, Zucker S, Cao J, et al. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs. FASEB J 2005; 19: 15071509.

    • Search Google Scholar
    • Export Citation
  • 26. Koho NM, Mykkänen AK, Reeben M, et al. Sequence variations and two levels of MCT1 and CD147 expression in red blood cells and gluteus muscle of horses. Gene 2012; 491: 6570.

    • Search Google Scholar
    • Export Citation
  • 27. Hagemann T, Wilson J, Kulbe H, et al. Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J Immunol 2005; 175: 11971205.

    • Search Google Scholar
    • Export Citation
  • 28. Venkatesan B, Valente AJ, Reddy VS, et al. Resveratrol blocks interleukin-18-EMMPRIN cross-regulation and smooth muscle cell migration. Am J Physiol Heart Circ Physiol 2009; 297: H874H886.

    • Search Google Scholar
    • Export Citation
  • 29. Knutti N, Kuepper M, Friedrich K. Soluble extracellular matrix metalloproteinase inducer (EMMPRIN, EMN) regulates cancer-related cellular functions by homotypic interactions with surface CD147. FEBS J 2015; 282: 41874200.

    • Search Google Scholar
    • Export Citation
  • 30. Tang Y, Kesavan P, Nakada MT, et al. Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res 2004; 2: 7380.

    • Search Google Scholar
    • Export Citation
  • 31. Clutterbuck AL, Harris P, Allaway D, et al. Matrix metalloproteinases in inflammatory pathologies of the horse. Vet J 2010; 183: 2738.

    • Search Google Scholar
    • Export Citation
  • 32. Barton AK, Shety T, Bondzio A, et al. Metalloproteinases and their tissue inhibitors in comparison between different chronic pneumopathies in the horse. Mediat Inflamm 2015; 2015: 569512.

    • Search Google Scholar
    • Export Citation
  • 33. Hughes KJ, Malikides N, Hodgson DR, et al. Comparison of tracheal aspirates and bronchoalveolar lavage in race-horses 1. Evaluation of cytological stains and the percentage of mast cells and eosinophils. Aust Vet J 2003; 81: 681684.

    • Search Google Scholar
    • Export Citation
  • 34. McGorum BC, Dixon PM. The analysis and interpretation of equine bronchoalveolar lavage fluid (BALF) cytology. Equine Vet Educ 1994; 6: 203209.

    • Search Google Scholar
    • Export Citation
  • 35. Nevalainen M, Raulo SM, Brazil TJ, et al. Inhalation of organic dusts and lipopolysaccharide increases gelatinolytic matrix metalloproteinases (MMPs) in the lungs of heaves horses. Equine Vet J 2002; 34: 150155.

    • Search Google Scholar
    • Export Citation
  • 36. Cundall M, Sun Y, Miranda C, et al. Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids. J Allergy Clin Immunol 2003; 112: 10641071.

    • Search Google Scholar
    • Export Citation
  • 37. Ohno I, Ohtani H, Nitta Y, et al. Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation. Am J Respir Cell Mol Biol 1997; 16: 212219.

    • Search Google Scholar
    • Export Citation
  • 38. Kirschvink N, Fiévez L, Dogné S, et al. Comparison of inulin with urea as dilutional markers of bronchoalveolar lavage in healthy and heaves-affected horses. Vet Res 2001; 32: 145154.

    • Search Google Scholar
    • Export Citation
  • 39. Haslam PL, Baughman R. Report of ERS Task Force: guidelines for measurement of acellular components and standardization of BAL. Eur Respir J 1999; 14: 245248.

    • Search Google Scholar
    • Export Citation

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Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and −9 in horses with chronic airway inflammation

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  • 1 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 2 Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 3 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 4 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 5 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.

Abstract

OBJECTIVE To examine whether expression of extracellular matrix metalloproteinase inducer (EMMPRIN) can be detected in equine lungs and whether it correlates with matrix metalloproteinase (MMP)-2 and -9 expression in bronchoalveolar lavage fluid (BALF) of horses with chronic inflammation of the lungs (ie, lower airway inflammation [LAI]).

ANIMALS 29 horses with signs of chronic respiratory tract disease, which were classified as the LAI (n = 17) and LAI with respiratory distress (RDLAI [12]) groups, and 15 control horses.

PROCEDURES BALF, tracheal aspirate, and blood samples were obtained, and EMMPRIN expression was determined from BALF cells and RBCs by use of western blotting. Activities of MMP-2 and -9 were determined with zymography.

RESULTS Expression of EMMPRIN protein was identified in BALF cells of all horses. Expression of EMMPRIN protein was highest for the RDLAI group and was correlated with MMP-2 and -9 protein expression, MMP-9 gelatinolytic activity, and airway neutrophilia.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that EMMPRIN was involved in the pathophysiologic processes of asthma in horses. However, additional studies of horses and other species are warranted to elucidate the regulation of EMMPRIN expression in asthmatic lungs.

Contributor Notes

Address correspondence to Dr. Rossi (heini.rossi@helsinki.fi).