Dose responses to inhalation of endotoxin, hay dust suspension and Aspergillus fumigatus extract in horses as measured by levels and activation of matrix metalloproteinase-9.

The research explores how different doses of certain substances affect levels and activation of specific enzymes within the airways of horses susceptible to a chronic lung condition. The substances in question include endotoxin, hay dust suspension, and an extract derived from a certain type of fungus. The results of the study indicate that the enzymes in question increase in response to exposure to these substances in a dose-dependent manner, suggesting the potential for enzyme inhibitors as a way to reduce lung inflammation.

Research Purpose

• The objective of the study was to observe the responses of two enzymes called matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) in the bronchoalveolar lavage fluid (BALF) of horses susceptible to a chronic lung condition known as “heaves”. Specifically, the researchers wanted to see how these enzymes reacted after the horses inhaled a hay dust suspension, endotoxin (also known as lipopolysaccharides or LPS), and an extract from the fungus Aspergillus fumigatus.

Methods

• The study involved both control horses and horses susceptible to heaves. All horses were exposed to specific doses of hay dust suspension and LPS. Additionally, the heave-susceptible horses were exposed to different doses of Aspergillus fumigatus extract.
• BALF collected after these inhalation challenges was analyzed using an analytical technique known as gelatin zymography. This technology helps identify the proteins, their forms and activity levels based on their molecular weights.

Results

• It was observed that all challenge substances induced a dose-dependent increase in proteolytic (protein-breaking) activity. This dose-dependent effect was most clear in the case of the proenzyme (inactive form) and active form of MMP-9 in heave-susceptible horses after exposure to LPS.
• There was a dose-dependent increase in MMP-9 content within the BALF of both control and heave-susceptible horses following exposure to organic dust and its components, with the highest increase seen in horses predisposed to heaves.
• The substances that horses inhaled had varying potential to trigger inflammation, making organic dust components important to consider for their differential pro-inflammatory capacity.

Conclusions

• The study confirms the role of matrix metalloproteinases in the development of heaves, a lung disease in horses. The dose-dependent increase of these enzymes upon exposure to dust-related substances sheds light on the mechanisms of lung inflammation in horses.
• Given this finding, protease inhibitors may be an effective way of reducing the lung inflammatory response in horses when they inhale organic dust. This paves the way for future research into therapeutic options designed to downregulate the activity of these enzymes in horse populations susceptible to heaves.