Abstract
SummaryReasons for performing studyAlveolar macrophages (AMs) are the first line of defence against pathogens in the lungs of all mammalian species and thus may constitute appropriate therapeutic target cells 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.ObjectivesTo compare the transcriptome of equine AMs with that of equine peritoneal macrophages (PMs) and to investigate the effect of lipopolysaccharide (LPS) on equine AM.Study designGene expression study of equine AMs.MethodsCells from both bronchoalveolar and peritoneal lavage fluid were isolated from systemically healthy horses that had been submitted to euthanasia. Cells were cryopreserved. RNA was extracted and comparative microarray analyses were performed in AMs and PMs, and in AMs treated and untreated with LPS. Comparisons with published data derived from human AM studies were made, with particular focus on LPS‐induced inflammatory status.ResultsThe 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 gene expression profile of equine AMs following LPS stimulation revealed significant changes in the expression of 240 genes, including well‐known upregulated inflammatory genes. This LPS‐induced gene expression profile of equine AMs more closely resembles that of human rather than murine macrophages.ConclusionsThis study improves current understanding of equine macrophage biology. These 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.
Highlights
The mucosal surface of the lung is continuously exposed to potential pathogens, proinflammatory particulates and inhaled toxins
We have previously identified and reported various functional and phenotypic differences between equine alveolar macrophages (AMs) and peritoneal macrophages (PMs) [4], to date no published data exist on such a comparison in the horse at the level of cellular global gene expression
Despite the common use of murine model-derived data to improve our understanding of human innate immunity, there is an ever-increasing appreciation that significant differences exist between man and mice with respect to the gene expression profiles associated with certain pathologies [6,7]
Summary
The mucosal surface of the lung is continuously exposed to potential pathogens, proinflammatory particulates and inhaled toxins. In addition to the barriers provided by surfactants and mucus, alveolar macrophages (AMs) provide a first line of immune defence and an efficient mechanism of particulate and pathogen clearance They play a key role in the initiation and propagation of both acute and chronic lung injury-induced pathology [1]. We have previously identified and reported various functional and phenotypic differences between equine AMs and peritoneal macrophages (PMs) [4], to date no published data exist on such a comparison in the horse at the level of cellular global gene expression. We consider this to be a natural progression from the previously identified differences between these cell populations. An appreciation of both similarities and dissimilarities between the equine AM and AMs derived from other species is a necessary prerequisite to the translation of data derived from other species to the horse, and vice versa
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