The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide

Kapétanovic, Ronan; Fairbairn, Lynsey; Downing, Alison; Beraldi, Dario; Sester, David P.; Freeman, Tom C.; Tuggle, Christopher K.; Archibald, Alan; Hume, David

doi:10.1186/1471-2164-14-581

Cited by 49 publications

(56 citation statements)

References 33 publications

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“…The greater expression of genes encoding TGFB1 , which plays a key role in alveolar homeostasis , and the C‐type lectin MRC1 , which is also highly expressed in porcine AMs , is supportive of a predominantly M2 (alternatively activated) phenotype in equine AMs, which may play a role in suppressing spontaneous and/or over‐exuberant inflammation in the lung . By contrast, the highly expressed transcripts identified in PMs may reflect either a classical [M1] ( CXCL1 , CXCL3 , IL1A , IL1B , IL8 , NFKB2 ) or an alternative [M2] ( CCL22 , IL4R , IL10 ) phenotype.…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptome analysis of equine alveolar macrophages

Karagianni

Kapétanovic

Summers

et al. 2016

Equine Veterinary Journal

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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.

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Section: Discussionmentioning

confidence: 99%

Comparative transcriptome analysis of equine alveolar macrophages

Karagianni

Kapétanovic

Summers

et al. 2016

Equine Veterinary Journal

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“…As in our previous CCl 4 and ozone exposure studies in rats, the experimental exposures and sample collections were all done in one laboratory under identical conditions. Göttingen mini pigs were chosen as a clinically relevant species, resembling humans in various functions as assessed by cardiovascular, respiratory, and biochemical parameters [10, 17, 18]. In addition, the use of larger animals as an LPS model of oxidative stress allowed their use as an internal control prior to treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The inflammatory response includes activation of free radical-generating enzymes in various types of cells that initiate host lipid peroxidation. In this study, LPS treatment of Göttingen mini pigs was chosen as a model of oxidative stress because the response of pig macrophages to LPS more closely resembles that of humans than mice in their set of macrophage-expressed systemic manifestations and LPS-inducible genes [10]. Therefore, the similarities between pigs and humans support the use of the pig as a more predictive model than the rodent in research studies [10].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress

Kadiiska

Peddada

Herbert

et al. 2015

Free Radical Biology and Medicine

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This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Göttingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point. Animals were injected with two doses of LPS at 2.5- and 5 μg/kg i.v. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2 h, 16 h, 48 h and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (α, δ, γ), ratios of GSH/GSSG, cysteine/cystine (Cys/CySS), mixed disulfides and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had harmful effect on liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidants concentrations making changes difficult to detect. Although this study used a mini pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models, that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.

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“…A study performed on five breeds of pig; Duroc, Píetrain, Landrace, Hampshire and Large White, found that the number of genes differentially expressed between these breeds in response to in vitro lipopolysaccharide was relatively small but included the immune-related genes Interleukin 12A (IL12A) and Colony Stimulating Factor 2 (CSF2) which were more abundantly expressed in Hampshire than Large White or Píetrain (Kapetanovic et al, 2013). In this latter study macrophage gene expression was also assessed with an Affymetrix Snowball Porcine Array, covering the entire transcriptome (Freeman et al, 2012).…”

Section: Molecular Biomarkers In Pigsmentioning

confidence: 99%

Molecular approaches to the diagnosis and monitoring of production diseases in pigs

Giles

Belkhiri

Barrow

et al. 2017

Research in Veterinary Science

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Production disease in pigs is caused by a variety of different pathogens, mainly enteric and respiratory and can result in significant economic loss. Other factors such as stress, poor husbandry and nutrition can also contribute to an animal's susceptibility to disease. Molecular biomarkers of production disease could be of immense value by improving diagnosis and risk analysis to determine best practice with an impact on increased economic output and animal welfare. In addition to the use of multiplex PCR or microarrays to detect individual or mixed pathogens during infection, these technologies can also be used to monitor the host response to infection via gene expression. The patterns of gene expression associated with cellular damage or initiation of the early immune response may indicate the type of pathology and, by extension the types of pathogen involved. Molecular methods can therefore be used to monitor both the presence of a pathogen and the host response to it during production disease. The field of biomarker discovery and implementation is expanding as technologies such as microarrays and next generation sequencing become more common. Whilst a large number of studies have been carried out in human medicine, further work is needed to identify molecular biomarkers in veterinary medicine and in particular those associated with production disease in the pig industry. The pig transcriptome is highly complex and still not fully understood. Further gene expression studies are needed to identify molecular biomarkers which may have predictive value in identifying the environmental, nutritional and other risk factors which are associated with production diseases in pigs.

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The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide

Cited by 49 publications

References 33 publications

Comparative transcriptome analysis of equine alveolar macrophages

Comparative transcriptome analysis of equine alveolar macrophages

Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress

Molecular approaches to the diagnosis and monitoring of production diseases in pigs

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