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- Author or Editor: Timo A. Sorsa x
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Abstract
Objectives—To determine whether samples of tracheal epithelial lining fluid (TELF) obtained from horses have elastinolytic activity characteristic of metalloproteinases, to compare elastinolytic activity in TELF obtained from healthy horses and horses with chronic obstructive pulmonary disease (COPD), and to determine whether chemically modified tetracycline-3 (CMT-3) inhibits elastinolytic activity in TELF.
Animals—10 horses with COPD and 10 healthy control horses.
Procedure—Zymography and fluorometry were used to measure elastinolytic activity, and EDTA was used to inhibit elastinolytic activity and verify that the activity was attributable to metalloproteinases. Possible inhibition of elastinolytic activity with CMT-3 was studied in vitro.
Results—Elastinolytic activity was found in TELF obtained from all horses, and this activity was significantly higher in TELF obtained from horses with COPD than in TELF obtained from healthy horses. For all samples, EDTA and CMT-3 inhibited elastinolytic activity.
Conclusions and Clinical Relevance—Elastinolytic activity is detectable in TELF obtained from horses and seems to be attributable to metalloproteinases. Elastinolytic activity in TELF is significantly inhibited by CMT-3. Elastinolytic activity in TELF can be detected by means of zymography or fluorometry. Increased elastinolytic activity may reflect destruction of pulmonary tissue in horses with COPD. Chemically modified tetracyclines such as CMT-3 may provide an additional treatment possibility for horses with COPD. (Am J Vet Res 2000;61:1067–1073)
Abstract
Objectives—To determine collagenase activity and evaluate matrix metalloproteinase (MMP)-8 and MMP-13 in horses with chronic obstructive pulmonary disease (COPD).
Animals—12 horses with COPD and 12 healthy control horses.
Procedure—Collagenase activity was determined by use of an assay for degradation of type-I collagen. Western immunoblot analysis was used to identify interstitial collagenases MMP-8 and MMP-13 in tracheal epithelial lining fluid (TELF). Immunocytochemistry and in situ hybridization were used to determine cellular expression of these 2 collagenases in cells in bronchoalveolar lavage fluid (BALF).
Results—Collagenase activity was approximately 7 times higher in samples obtained from horses with COPD, compared with control horses. During stabling, horses with COPD had significantly higher collagenase activity than after being maintained on summer pasture, when activity was similar to that of control horses. Immunoreactivity of MMP-8 and MMP-13 was significantly increased in TELF of horses with COPD, compared with healthy horses. In TELF, a positive correlation was detected between immunoreactivity of MMP-8 and MMP-13 and the amount of degradation of type-I collagen. Macrophages and epithelial cells were the major cellular sources of MMP-8 and MMP-13.
Conclusions and Clinical Relevance—Increased collagenase activity in TELF indicates active ongoing disease and, thus, may reflect lung tissue changes in horses with COPD. Measurements of collagenase activity and MMP immunoreactivity may provide additional diagnostic tools to identify the active phase of chronic lung disease. (Am J Vet Res 2001;62:1142–1148)
