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Home / Equine Research Bank / Acta Vet Scand / Collagenolytic activity and its sensitivity to doxycycline i...
Acta veterinaria Scandinavica1997; 38(1); 9-16; doi: 10.1186/BF03548503

Collagenolytic activity and its sensitivity to doxycycline inhibition in tracheal aspirates of horses with chronic obstructive pulmonary disease.

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 1 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.
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Publication Date: 1997-01-01 PubMed ID: 9129342PubMed Central: PMC8057019DOI: 10.1186/BF03548503Google Scholar: Lookup
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  • Journal Article
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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 article investigates the activity of collagen-digesting enzymes in the respiratory tract of horses with chronic obstructive pulmonary disease (COPD) and their responsiveness to the drug doxycycline. The results suggest potential therapeutic benefits of drugs that inhibit these enzymes in treating equine COPD.

Collagenolytic Activity in Horses with COPD

  • This study focused on the activity of enzymes that degrade collagen (a protein that provides structure and strength to tissues) in the tracheal aspirates (TA) of horses with COPD. Using a lab technique known as SDS-PAGE gel electrophoresis, the researchers measured this collagenolytic activity in the respiratory tract mucus or fluid produced by horses with this lung disease.
  • The results showed that both automated and total collagenase (the specific enzyme that break down collagen) activity were significantly higher in horses suffering from symptomatic COPD than in healthy horses.

Sensitivity of Collagenolytic Activity to Doxycycline

  • Doxycycline, an antibiotic often used to treat bacterial infections, is also known to inhibit the activity of certain collagenases.
  • In this study, the team investigated how responsive the elevated collagenolytic activity in COPD-affected horses was to doxycycline treatment and found that doxycycline indeed effectively inhibited it.
  • The researchers were able to identify and suggest that most of the collagenase activity was due to a type of collagenase produced by neutrophils (a type of white blood cell), known as MMP-8.
  • However, they also found that some activity was due to collagenases derived from other cells such as fibroblasts (connective tissue cells), monocyte/macrophages (another type of white blood cell) and bacteria.

Potential Therapeutic Implications

  • Based on these findings, the researchers suggested that drugs that inhibit collagenases could potentially be useful in the treatment of COPD in horses.
  • The evidenced response to doxycycline suggests that this drug or other similar drugs could be an effective treatment alternative worth exploring further.

Cite This Article

APA
Koivunen AL, Maisi P, Konttinen YT, Prikk K, Sandholm M. (1997). Collagenolytic activity and its sensitivity to doxycycline inhibition in tracheal aspirates of horses with chronic obstructive pulmonary disease. Acta Vet Scand, 38(1), 9-16. https://doi.org/10.1186/BF03548503

Publication

Acta veterinaria Scandinavica
ISSN: 0044-605X
NlmUniqueID: 0370400
Country: England
Language: English
Volume: 38
Issue: 1
Pages: 9-16

Researcher Affiliations

Koivunen, A L
  • Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland.
Maisi, P
    Konttinen, Y T
      Prikk, K
        Sandholm, M

          MeSH Terms

          • Animals
          • Collagen / metabolism
          • Collagenases / isolation & purification
          • Collagenases / metabolism
          • Doxycycline / pharmacology
          • Electrophoresis, Polyacrylamide Gel
          • Horse Diseases
          • Horses
          • Lung Diseases, Obstructive / enzymology
          • Lung Diseases, Obstructive / veterinary
          • Matrix Metalloproteinase Inhibitors
          • Mucous Membrane / enzymology
          • Suction
          • Trachea

          References

          This article includes 30 references
          1. Campbell EJ, Senior RM, Welgus HG. Extracellular matrix injury during lung inflammation.. Chest 1987 Jul;92(1):161-7.
            doi: 10.1378/chest.92.1.161pubmed: 3036424google scholar: lookup
          2. Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby P. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions.. Ann N Y Acad Sci 1995 Jan 17;748:501-7.
            doi: 10.1111/j.1749-6632.1994.tb17348.xpubmed: 7695193google scholar: lookup
          3. 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 May 15;261(14):6600-5.
            pubmed: 3009463
          4. 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 Aug;66(8):1310-4.
            doi: 10.1177/00220345870660080401pubmed: 3040832google scholar: lookup
          5. 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(3):297-321.
            doi: 10.1177/10454411910020030201pubmed: 1654139google scholar: lookup
          6. Golub LM, Suomalainen K, Sorsa T. Host modulation with tetracyclines and their chemically modified analogues.. Curr Opin Dent 1992 Mar;2:80-90.
            pubmed: 1325849
          7. Grant GA, Goldberg GI, Wilhelm SM, He C, Eisen AZ. Activation of extracellular matrix metalloproteases by proteases and organomercurials.. Matrix Suppl 1992;1:217-23.
            pubmed: 1480030
          8. Grunig G, Hermann M, Von Fellenberg R. Protease and antiprotease activity in the respiratory secretions of horses suffering from COPD. Lung function and respiratory diseases in the horse 1985;pp. 29–31.
          9. Guttmann I, Bergmayer HU. Determination of urea with glutamate dehydrogenase as indicator enzyme. Methods of enzymatic analysis 2nd ed. 1974;pp. 1794–1798.
          10. Koivunen AL, Maisi P, Fang W, Sandholm M. Inhibition of the protease activity in tracheobronchial aspirates of horses with chronic obstructive pulmonary disease.. Am J Vet Res 1996 May;57(5):603-7.
            pubmed: 8723867
          11. Koivunen AL, Maisi P, Konttinen YT, Sandholm M. Gelatinolytic activity in tracheal aspirates of horses with chronic obstructive pulmonary disease.. Acta Vet Scand 1997;38(1):17-27.
            pmc: PMC8057023pubmed: 9129343doi: 10.1186/bf03548504google scholar: lookup
          12. Konttinen YT, Kangaspunta P, Lindy O, Takagi M, Sorsa T, Segerberg M, Tschesche H, Eisen AZ. Collagenase in Sjögren's syndrome.. Ann Rheum Dis 1994 Dec;53(12):836-9.
            doi: 10.1136/ard.53.12.836pmc: PMC1005486pubmed: 7864694google scholar: lookup
          13. Lauhio A, Konttinen YT, Tschesche H, Nordström D, Salo T, Lähdevirta J, Golub LM, Sorsa T. Reduction of matrix metalloproteinase 8-neutrophil collagenase levels during long-term doxycycline treatment of reactive arthritis.. Antimicrob Agents Chemother 1994 Feb;38(2):400-2.
            doi: 10.1128/AAC.38.2.400pmc: PMC284468pubmed: 8192476google scholar: lookup
          14. Lauhio A, Sorsa T, Lindy O, Suomalainen K, Saari H, Golub LM, Konttinen YT. The anticollagenolytic potential of lymecycline in the long-term treatment of reactive arthritis.. Arthritis Rheum 1992 Feb;35(2):195-8.
            doi: 10.1002/art.1780350211pubmed: 1310409google scholar: lookup
          15. MacNamara B, Bauer S, Iafe J. Endoscopic evaluation of exercise-induced pulmonary hemorrhage and chronic obstructive pulmonary disease in association with poor performance in racing Standardbreds.. J Am Vet Med Assoc 1990 Feb 1;196(3):443-5.
            pubmed: 2298674
          16. Mainardi CL, Pourmotabbed TF, Hasty KA. Inflammatory phagocytes and connective tissue degrading metalloproteinases.. Am J Med Sci 1991 Sep;302(3):171-5.
            doi: 10.1097/00000441-199109000-00010pubmed: 1928227google scholar: lookup
          17. Miller EJ, Rhodes KR. Preparation and characterization of the different Types of collagen. Structural and contractile proteins, part A: Methods in enzymology 1982.
          18. Moscatelli D, Rifkin DB. Membrane and matrix localization of proteinases: a common theme in tumor cell invasion and angiogenesis.. Biochim Biophys Acta 1988 Aug 3;948(1):67-85.
            pubmed: 2456098doi: 10.1016/0304-419x(88)90005-4google scholar: lookup
          19. Rennard SI, Basset G, Lecossier D, O'Donnell KM, Pinkston P, Martin PG, Crystal RG. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution.. J Appl Physiol (1985) 1986 Feb;60(2):532-8.
            doi: 10.1152/jappl.1986.60.2.532pubmed: 3512509google scholar: lookup
          20. Rossdale PD, Hopes R, Digby NJ, offord K. Epidemiological study of wastage among racehorses 1982 and 1983.. Vet Rec 1985 Jan 19;116(3):66-9.
            doi: 10.1136/vr.116.3.66pubmed: 3976145google scholar: lookup
          21. Saari H, Suomalainen K, Lindy O, Konttinen YT, Sorsa T. Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases.. Biochem Biophys Res Commun 1990 Sep 28;171(3):979-87.
            doi: 10.1016/0006-291X(90)90780-Qpubmed: 2171513google scholar: lookup
          22. Sepper R, 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 Jun;107(6):1641-7.
            doi: 10.1378/chest.107.6.1641pubmed: 7781360google scholar: lookup
          23. Shapiro SD, Campbell EJ, Senior RM, Welgus HG. Proteinases secreted by human mononuclear phagocytes.. J Rheumatol Suppl 1991 Feb;27:95-8.
            pubmed: 1902875
          24. Sorsa T, Ingman T, Suomalainen K, Haapasalo M, Konttinen YT, Lindy O, Saari H, Uitto VJ. Identification of proteases from periodontopathogenic bacteria as activators of latent human neutrophil and fibroblast-type interstitial collagenases.. Infect Immun 1992 Nov;60(11):4491-5.
            doi: 10.1128/IAI.60.11.4491-4495.1992pmc: PMC258193pubmed: 1398963google scholar: lookup
          25. Sorsa T, Lindy O, Konttinen YT, Suomalainen K, Ingman T, Saari H, Halinen S, Lee HM, Golub LM, Hall J. Doxycycline in the protection of serum alpha-1-antitrypsin from human neutrophil collagenase and gelatinase.. Antimicrob Agents Chemother 1993 Mar;37(3):592-4.
            doi: 10.1128/AAC.37.3.592pmc: PMC187711pubmed: 8384819google scholar: lookup
          26. Suomalainen K, Sorsa T, Golub LM, Ramamurthy N, Lee HM, Uitto VJ, Saari H, Konttinen YT. Specificity of the anticollagenase action of tetracyclines: relevance to their anti-inflammatory potential.. Antimicrob Agents Chemother 1992 Jan;36(1):227-9.
            doi: 10.1128/AAC.36.1.227pmc: PMC189275pubmed: 1317148google scholar: lookup
          27. Turto H, Lindy S, Uitto VJ, Wegelius O, Uitto J. Human leukocyte collagenase: characterization of enzyme kinetics by a new method.. Anal Biochem 1977 Dec;83(2):557-69.
            doi: 10.1016/0003-2697(77)90059-8pubmed: 203207google scholar: lookup
          28. Weiss SJ. Tissue destruction by neutrophils.. N Engl J Med 1989 Feb 9;320(6):365-76.
            pubmed: 2536474doi: 10.1056/nejm198902093200606google scholar: lookup
          29. Werb Z, Gordon S. Secretion of a specific collagenase by stimulated macrophages.. J Exp Med 1975 Aug 1;142(2):346-60.
            doi: 10.1084/jem.142.2.346pmc: PMC2189891pubmed: 167095google scholar: lookup
          30. Woessner JF Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling.. FASEB J 1991 May;5(8):2145-54.
            doi: 10.1096/fasebj.5.8.1850705pubmed: 1850705google scholar: lookup

          Citations

          This article has been cited 6 times.
          1. Barton AK, Shety T, Klier J, Geis S, Einspanier R, Gehlen H. Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma.. Mediators Inflamm 2019;2019:7845623.
            doi: 10.1155/2019/7845623pubmed: 31316303google scholar: lookup
          2. Barton AK, Gehlen H. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?. Mediators Inflamm 2016;2016:5693205.
            doi: 10.1155/2016/5693205pubmed: 28053371google scholar: lookup
          3. Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H. Metalloproteinases and their inhibitors are influenced by inhalative glucocorticoid therapy in combination with environmental dust reduction in equine recurrent airway obstruction.. BMC Vet Res 2016 Dec 9;12(1):282.
            doi: 10.1186/s12917-016-0915-1pubmed: 27938355google scholar: lookup
          4. Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H. Metalloproteinases and Their Tissue Inhibitors in Comparison between Different Chronic Pneumopathies in the Horse.. Mediators Inflamm 2015;2015:569512.
            doi: 10.1155/2015/569512pubmed: 26770019google scholar: lookup
          5. Dalvi PS, Singh A, Trivedi HR, Ghanchi FD, Parmar DM, Mistry SD. Effect of doxycycline in patients of moderate to severe chronic obstructive pulmonary disease with stable symptoms.. Ann Thorac Med 2011 Oct;6(4):221-6.
            doi: 10.4103/1817-1737.84777pubmed: 21977068google scholar: lookup
          6. Art T, Franck T, Lekeux P, de Moffarts B, Couëtil L, Becker M, Kohnen S, Deby-Dupont G, Serteyn D. Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses and those with recurrent airway obstruction.. Can J Vet Res 2006 Oct;70(4):291-6.
            pubmed: 17042382
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