Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma-like equine disease.

This study investigates the role of pulmonary intravascular macrophages (PIMs) in the development of heaves, an asthma-like disease of horses triggered by dust. Results suggest in horses, PIMs increase the inflammatory response, including a greater migration of neutrophils and expressions of proinflammatory molecules in the bronchoalveolar lavage (BAL) cells.

Research Aim

• The primary objective of this study was to examine the role of pulmonary intravascular macrophages (PIMs) in causing heaves, which is an obstructive neutrophilic airway inflammation in horses. It shows similarities to human asthma and is usually triggered by elements found in dust, such as endotoxin.

Methods

• Nine mares were exposed to either alfalfa cubes (Cb), alfalfa cubes along with gadolinium chloride (GC) to deplete PIMs (Cb-GC), moldy hay (MH) to induce heaves, or moldy hay along with GC (MH-GC).
• Subsequently, the clinical scores and concentrations of neutrophils, a type of white blood cell, in the bronchoalveolar lavage (BAL) fluid of these horses were evaluated.
• The research also examined IL-8 (a chemokine involved in inflammation) and TLR4 (a receptor activated by endotoxin) mRNA expression in the BAL cells.
• Additionally, the BAL cells were subjected to an LPS challenge in vitro to study the change in IL-8 and TLR4 mRNA expression.

Results

• The horses exposed to moldy hay exhibited higher clinical scores and neutrophil concentrations in the lavage fluid compared to those treated with the PIM-depleting gadolinium chloride (MH-GC).
• The BAL cells from MH-GC treated horses showed significantly lower levels of IL-8 and TLR4 mRNA expressions compared with horses exposed to moldy hay alone.
• When BAL cells were challenged with LPS in vitro, there was a significant increase in IL-8 but not TLR4 mRNA expression in cells recovered from horses fed with moldy hay. No such increase was observed in the cells from the MH-GC treatment group.

Summary

• The results suggest that depleting PIMs in horses reduced clinical symptoms of heaves and decreased the migration of neutrophils into the alveoli. It also diminished the expression of proinflammatory molecules like IL-8 and TLR4 mRNA in the BAL cells of heaves-affected horses.
• Therefore, the research proposes that PIMs play a proinflammatory role in the development of this airborne disease, making them potential targets for therapeutic interventions for heaves.