MMP-9 as a marker of inflammation in tracheal epithelial lining fluid (TELF) and in bronchoalveolar fluid (BALF) of COPD horses.

The research study analyses gelatinolytic activity in horses with chronic obstructive pulmonary disease (COPD) to understand if the elevated activity found in the respiratory tract of these horses could also be present at the lower part of the tract. The study suggests that MMP-9, a type of matrix metalloproteinase, could serve as a potential diagnostic marker for COPD in horses.

Objective of the Research

• The primary objective of this research was to analyze whether the elevated gelatinolytic activity previously found at the tracheal level of horses with COPD could also be seen at the lower part of the respiratory tract.
• The study also aimed to determine the presence and significance of gelatinolytic matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the respiratory secretions of healthy and COPD horses.

Findings of the Research

• High levels of gelatinolytic matrix metalloproteinases were detected in bronchoalveolar and tracheobronchial secretions from horses with COPD.
• Of these MMPs, MMP-9 showed significant pathological elevation.
• Increased activities of MMP-9 were detected in all respiratory samples from COPD horses when compared to healthy horses, as evaluated by gelatin zymography and Western blotting techniques.
• An increase in the active form of MMP-9 was correlated with elevated levels of gelatinase-associated lipocalin.
• BALF epithelial cells, macrophages, neutrophils, and lymphocytes demonstrated MMP-9 immunoreactivity. The expression of MMP-9 mRNA was detected by bronchial epithelial cells, as evidenced by in situ hybridization.
• Significantly, no major role in chronic lung inflammation was found to be played by MMP-2. There were no clear differences in the levels of MMP-2 or MMP-14 (a potent activator of MMP-2) when samples from COPD horses were compared to those from healthy horses.

Implications of the Research

• MMP-9 could potentially serve as a diagnostic marker for the active ongoing tissue remodeling seen in the acute phase of equine COPD. This suggests new, meaningful avenues for detecting and potentially managing this condition in horses.
• The increased gelatinolytic activity indicative of ongoing tissue damage in COPD could be found at both tested respiratory tract levels: the bronchoalveolar and the tracheobronchial levels.
• Tracheal epithelial lining fluid (TELF) samples were identified as valuable diagnostic materials for detecting increased levels of the main gelatinolytic MMP, MMP-9, thereby representing the entire diseased lung and providing a more comprehensive diagnostic picture.