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Collagenolytic Activity and its Sensitivity to Doxycycline Inhibition in Tracheal Aspirates of Horses with Chronic Obstructive Pulmonary Disease

Acta Veterinaria Scandinavica volume 38, pages 9–16 (1997)Cite this article

Abstract

The collagenolytic activity and its sensitivity to doxycycline inhibition in tracheal aspirates (TA) of horses with chronic obstructive pulmonary disease (COPD) was analyzed with SDS-PA gel electrophoresis (SDS-PAGE), using Type I collagen as the substrate. Both autoactive and total collagenase activities were significantly higher in TAs of horses with symptomatic COPD than in TAs of healthy horses. Doxycycline inhibition studies suggest that most of the TA collagenase is of the neutrophil type (MMP-8), but some is derived from other cells such as fibroblasts and monocyte/macrophages (MMP-1) and bacteria (bacterial collagenases). Drugs inhibiting collagenases in the respiratory tract might be worth a trial in the treatment of COPD in horses.

References

  • Campbell EJ, Senior RM, Welgus HG: Extracellular matrix injury during lung inflammation. Chest 1987, 92, 161–167.

    Article  CAS  Google Scholar 

  • Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby B: Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann. N. Y. Acad. Sci. 1995, 748, 501–507.

    Article  CAS  Google Scholar 

  • Goldberg GI, Wilhelm SM, Kronberger A, Bauer EA, Grant GA, Eisen AZ: Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein. J. Biol. Chem. 1986, 261, 6600–6605.

    CAS  PubMed  Google Scholar 

  • Golub LM, McNamara TF, D‘Angelo G, Greenwald RA, Ramamurthy NS: A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity. J. Dent. Res. 1987, 66, 1310–1314.

    Article  CAS  Google Scholar 

  • Golub LM, Ramamurthy NS, McNamara TF, Greenwald RA, Rifkin BR: Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit. Rev. Oral Biol. Med. 1991, 2, 297–321.

    Article  CAS  Google Scholar 

  • Golub LM, Suomalainen K, Sorsa T: Host modulation with tetracyclines and their chemically modified analogues. Curr. Opi. Dent. 1992, 2, 80–90.

    CAS  Google Scholar 

  • Grant GA, Goldberg GI, Wilhelm SM, He C, Eisen AZ: Activation of extracellular matrix metalloproteases by proteases and organomercurials. Matrix 1992, Suppl. 1, 217–223.

    Google Scholar 

  • Grunig G, Hermann M, Von Fellenberg R: Protease and antiprotease activity in the respiratory secre- tions of horses suffering from COPD. In: Deegen E., Beadle RE, (ed.). Lung function and respiratory diseases in the horse. International Symposium in Hannover, Germany, June 27-29, 1985, Hippiatrica, Stuttgart, Germany, pp. 29–31.

    Google Scholar 

  • Guttmann I, Bergmayer HU: Determination of urea with glutamate dehydrogenase as indicator enzyme. In: Bergmayer, HU. (ed.): Methods of enzymatic analysis. 2nd ed. Academic Press, New York. 1974, pp. 1794–1798.

    Google Scholar 

  • Koivunen A-L, Maisi P, Fang W, Sandholm M: Inhibition of the protease activity in tracheobronchial aspirates of horses with chronic obstructive pulmonary disease. Amer. J. vet. Res. 1996, 57, 603–607.

    CAS  Google Scholar 

  • Koivunen A-L, Maisi P, Konttinen YT, Sandholm M: Gelatinolytic activity in tracheal aspirates of horses with chronic obstructive pulmonary disease. Acta vet. scand. 1997, 17–27.

    Google Scholar 

  • Konttinen YT, Kangaspunta P, Lindy O, Takagi M, Sorsa T, Segerberg M, Eisen AZ, Tschesche H: Collagenase in Sjogren’s syndrome. Ann. Rheum. Dis. 1994, 53, 836–839.

    Article  CAS  Google Scholar 

  • Lauhio A, Konttinen YT, Tschesche H, Nordstrom D, Salo T, Lahdevirta J, Golub LM, Sorsa T: Reduction of matrix metalloproteinase 8 -neutrophil collagenase levels during long-term doxycycline treatment reactive arthritis. Antimicrob. Agents Chemother. 1994, 38, 400–402.

    Article  CAS  Google Scholar 

  • Lauhio A, Sorsa T, Lindy O, Suomalainen K, Saari H, Golub LM, Konttinen YT: The anticollagenolytic potential of lymecycline in long-term treatment of reactive arthritis. Arthritis Rheum. 1992, 35, 195–198.

    Article  CAS  Google Scholar 

  • MacNamara B, Bauer S, Lafe J: Endoscopic evaluation of exercise-induced pulmonary haemorrhage and chronic obstructive pulmonary disease in association with poor performance in racing Stan- dardbreds. J. Amer. vet. med. Assoc. 1990, 196, 443–445.

    CAS  Google Scholar 

  • Mainardi CL, Pourmotabbed TF, Hasty KA: Inflammatory phagocytes and connective tissue degrading metalloproteinases. Amer. J. med. Sci. 1991, 302, 171–175.

    Article  CAS  Google Scholar 

  • Miller EJ, Rhodes KR: Preparation and characterization of the different Types of collagen. In: Cuningham LW, Fredriksen DW (eds.): Structural and contractile proteins, part A: Methods in enzymology. New York: Academic Press, 1982.

    Google Scholar 

  • Moscatelli D, Rifkin DB: Membrane and matrix localization of proteinases: A common theme in tumour cell invasion and angiogenesis. Biochem. Biophys. Acta 1988, 948, 67–85.

    CAS  PubMed  Google Scholar 

  • Rennard SSI, Basset G, Lecossier D, Donnel KM, Pinkston P, Martin P, Crystal RG: Estimation of volume of epithelial lining fluid recovered by lavage by using urea as a marker of dilution. J. Appl. Physiol. 1986, 60, 532–538.

    Article  CAS  Google Scholar 

  • Rossdale PD, Hopes R, Digby NJ, Offord K: Epidemiological study of wastage among racehorses 1982 and 1983. Vet. Rec. 1985, 116, 66–69.

    Article  CAS  Google Scholar 

  • Saari H, Suomalainen K, Lindy O, Konttinen YT, Sorsa T: Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteinases. Biochem. Biophys. Res. Com- mun. 1990, 171, 979–987.

    Article  CAS  Google Scholar 

  • Sepper RY, Konttinen YT, Ding Y, Takagi M, Sorsa T: Human neutrophil collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease. Chest 1995, 107, 1641–1647.

    Article  CAS  Google Scholar 

  • Shapiro SD, Campbell EJ, Senior RM, Welgus HG: Proteinases secreted by human mononuclear phagocytes. J. Rheumatol. 1991, (Suppl. 27) 18, 95-98.

    Google Scholar 

  • Sorsa T, Ingman T, Suomalainen K, Haapasalo M, Konttinen YT, Lindy O, Saari H, Uitto V-J: Identification of proteinases from periodontopatho- genic bacteria as activators of latent human neutrophil and fibroblast-Type interstitial collagenases. Infect. Immun. 1992, 60, 4491–4495.

    Article  CAS  Google Scholar 

  • Sorsa T, Lindy O, Konttinen YT, Suomalainen K, Ingman T, Saari H, Halinen S, Lee H-M, Golub LM, Hall J, Simon S: Doxycycline in the protection of serum alpha-1-antitrypsin from human neutrophil collagenase and gelatinase. Antimicrob. Agents Chemother. 1993, 37, 592–594.

    Article  CAS  Google Scholar 

  • Suomalainen K, Sorsa T, Golub LM, Ramamurthy N, Lee H-M, Uitto V-J, Saari H, Konttinen YT: Specificity of the anti-collagenase action of tetracyclines: relevance to their anti-inflammatory potential. Antimicrob. Agents Chemother. 1992, 36, 227–229.

    Article  CAS  Google Scholar 

  • Turto H, Lindy S, Uitto V-J, Wegelius O, Uitto J: Human leukocyte collagenase: characterization of enzyme kinetics by a new method. Anal. Biochem. 1977, 83, 557–569.

    Article  CAS  Google Scholar 

  • Weiss SJ: Tissue destruction by neutrophils. N. Engl. J. Med. 1989, 320, 365–376.

    CAS  Google Scholar 

  • Werb Z, Gordon S: Secretion of a specific collagenase by stimulated macrophages. J. Exp. Med. 1975, 142, 346–360.

    Article  CAS  Google Scholar 

  • Woessner JF: Matrix metalloproteinases and their inhibitors in connective tissue remodelling. FASEB J. 1991, 5, 2145–2154.

    Article  CAS  Google Scholar 

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Acknowledgment

This study was supported by the Faculty of Veterinary Medicine, University of Helsinki, Emil Aaltonen foundation, the Academy of Finland, Helsinki University Central Hospital and Astra Research Foundation.

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Authors and Affiliations

  1. Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, Hämeentie 57, Helsinki, FIN-00014, Finland

    A.-L. Koivunen, P. Maisi & M. Sandholm

  2. Division of Rheumatic Disease, Department of Medicine, University Central Hospital, Helsinki, Finland

    Y. T. Konttinen & K. Prikk

Authors
  1. A.-L. Koivunen
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  2. P. Maisi
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  3. Y. T. Konttinen
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  4. K. Prikk
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  5. M. Sandholm
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Correspondence to P. Maisi.

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Koivunen, AL., Maisi, P., Konttinen, Y.T. et al. Collagenolytic Activity and its Sensitivity to Doxycycline Inhibition in Tracheal Aspirates of Horses with Chronic Obstructive Pulmonary Disease. Acta Vet Scand 38, 9–16 (1997). https://doi.org/10.1186/BF03548503

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Acta Veterinaria Scandinavica

ISSN: 1751-0147