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Reasons for performing study Alveolar 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. Objectives To 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 design Gene expression study of equine AMs. Methods Cells 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. 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 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. Conclusions This 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. [ABSTRACT FROM AUTHOR]

Summary Background Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. Objective To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction. Methods We measured the response of six heaves horses following inhalation of saline (placebo) and three doses of Aspergillus fumigatus extract. We then compared the response of six heaves horses to A. fumigatus extract inhalation before and after lipopolysaccharide (LPS) depletion. Results Inhalation challenge with 0.5, 1.6 and 5 mg of A. fumigatus extract resulted in a significant increase in bronchoalveolar lavage fluid (BALF) neutrophil ratio when compared with saline inhalation. Only 1.6 and 5 mg extract inhalation resulted in significant lung dysfunction compared with saline. There was no significant difference between 1.6 and 5 mg extract inhalation with respect to airway neutrophil numbers or lung function, suggesting a plateau in both measured responses. LPS depletion of 1.6 mg A. fumigatus extract resulted in a significant reduction in airway neutrophil numbers and increase in arterial oxygen tension. There was no significant difference between saline and the LPS-depleted A. fumigatus extract challenges with respect to neutrophil count and lung function. The reduction in airway neutrophil numbers was greater than would be predicted by extrapolation from previously reported soluble LPS dose–response inhalation experiments. Conclusion This study supports a role for other inhalants, in addition to soluble components of A. fumigatus , in the aetiopathogenesis of heaves. Also the amplification in response to LPS when inhaled with A. fumigatus extract, suggests that the role of inhaled endotoxin in the pulmonary inflammation and dysfunction in naturally occurring heaves may currently be underestimated. [ABSTRACT FROM AUTHOR]

Discusses clinicopathological features consistent with both botulism and grass sickness in foal. Etiology of equine grass sickness (EGS); Clinical diagnosis of toxicoinfectious botulism; Postmortem feature of toxicoinfectius botulism.

Aims To conduct a pilot study to inform sample size and trial methodology for a proposed triple-blinded randomised placebo-controlled field trial for a Clostridium botulinum type C toxoid vaccine in the prevention of equine grass sickness (EGS). Methods Only healthy horses/ponies residing on premises previously affected by a high incidence and frequency of EGS were included. Enrolled horses/ponies were randomly allocated, at premises-level, stratified by age, to vaccine or placebo treatment groups at a 1:1 ratio. Baseline and follow-up premises and horse data were obtained via telephone questionnaires. Veterinary surgeons responsible for the primary care of enrolled animals administered the primary course of vaccine/placebo on Days 0, 21, 42. Following appropriate training, owners completed post treatment daily observations for 7 days following each treatment. Results There were 5 participating practices, recruiting 10 EGS-affected premises in eastern Scotland. A total of 109 horses/ponies were enrolled: 13 were excluded prior to randomisation, and one was excluded following randomisation due to absence of a valid passport. Median age at enrolment was 5.5 years. Age (P = 0.34), gender (P = 0.19) and breed (P = 0.94) distributions did not differ significantly between vaccine and placebo groups. Ninety-five horses/ponies completed the primary treatment course. No significant adverse events were reported and overall prevalence of minor injection site reactions was 1.4% (n = 4/285; 95% CI 0.4-2.8%). Conclusions and practical significance Participant compliance has been excellent, and findings of this pilot study will be used to refine sample size calculations and inform modifications to trial methodology for a proposed future full-scale vaccine trial. Ethical animal research This study was conducted under an Animal Test Certificate and granted institutional ethical approval. Informed written owner consent was obtained for each animal, and procedures were in line with recognised veterinary practice as defined in The Animals (Scientific Procedures) Act 1986. Sources of funding: This study was generously funded by Neogen Corporation. Competing interests: None. [ABSTRACT FROM AUTHOR]