Comparative transcriptome analysis of equine alveolar macrophages

REASONS FOR PERFORMING STUDY: Alveolar macrophages (AMs) are the first line of defense against pathogens in the lungs of all mammalian species and therefore may constitute an appropriate therapeutic target cell in the treatment and prevention of opportunistic airway infections. Therefore, acquiring a better understanding of equine macrophage biology is of paramount importance in addressing this issue in relation to the horse.

STUDY DESIGN: Gene expression study of the equine AM.

OBJECTIVES: To compare the transcriptome of equine AMs to that of equine peritoneal macrophages (PMs) and investigate the effect of lipopolysaccharide (LPS) on the equine AM.

METHODS: Cells were isolated and cryopreserved from both bronchoalveolar and peritoneal lavage fluid from systemically healthy horses after euthanasia. RNA was extracted and comparative microarray analyses were performed between AMs and PMs, and between LPS treated and untreated AMs. Comparisons were also made with published data derived from human AM studies, with particular focus on their LPS induced inflammatory status.

RESULTS: The comparison between AMs and PMs revealed the differential basal expression of 451 genes. Gene expression analysis revealed an alternative (M2) macrophage polarisation profile in AMs and a hybrid macrophage activation profile in PMs, a phenomenon potentially attributable to a degree of induced endotoxin tolerance. The change in gene expression profile of equine AMs following LPS stimulation revealed a significant change in the expression of 240 genes, including well known upregulated inflammatory genes. This LPS induced gene expression profile of equine AMs more closely resembled that of human macrophages than murine macrophages.

CONCLUSIONS: This study improves our understanding of equine macrophage biology. Our data suggest that the horse may represent a suitable animal model for the study of human macrophage-associated lung inflammation and data derived from human macrophage studies may have significant relevance to the horse. This article is protected by copyright. All rights reserved.