M. C. Shepherd

University of Glasgow, Glasgow, Scotland, United Kingdom

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Publications (3)21.45 Total impact

  • Thorax 11/2012; 67(Suppl 2):A65-A66. DOI:10.1136/thoraxjnl-2012-202678.146 · 8.56 Impact Factor
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    ABSTRACT: Dendritic cells (DCs) are crucial for the processing of antigens, T lymphocyte priming and the development of asthma and allergy. Smokers with asthma display altered therapeutic behaviour and a reduction in endobronchial DC CD83 expression compared with non-smokers with asthma. No information is available on the impact of smoking on peripheral blood DC profiles. Determine peripheral blood DC profiles in subjects with and without asthma with differing smoking histories. Forty-three asthmatics (17 smokers, nine ex-smokers and 17 never-smokers) and 16 healthy volunteers (nine smokers and seven never-smokers) were recruited. Spirometry, exhaled nitric oxide and venesection was performed. DC elution was by flow cytometry via the expression of DC surface markers [plasmacytoid (pDC) (BDCA-2, CD303), type 1 conventional (cDC) (BDCA-1, CD1c), and type 2 cDC (BDCA-3, CD141)]. Subjects with asthma displayed increases in all DC subtypes compared with normal never-smokers: [type 1 cDCs - asthma [median% (IQR)]: 0.59% (0.41, 0.74), normal never-smokers: 0.35% (0.26, 0.43), P=0.013]; type 2 cDCs - asthma: 0.04% (0.02, 0.06), normal never-smokers: 0.02% (0.01, 0.03), P=0.008 and pDCs - asthma: 0.32% (0.27, 0.46), normal never-smokers: 0.22% (0.17, 0.31), P=0.043, and increased pDC and type 1 cDCs compared with normal smokers. Smoking did not affect DC proportions in asthma. Cigarette smoking reduced pDC proportions in normal subjects [normal never-smokers: 0.22% (0.17, 0.31); normal smokers: 0.09% (0.08, 0.15), P=0.003]. This study shows for the first time that subjects with asthma display a large increase in peripheral blood DC proportions. Cigarette smoking in asthma did not affect the peripheral blood DC profile but did suppress pDC proportions in non-asthmatic subjects. Asthma is associated with a significant increase in circulating DCs, reflecting increased endobronchial levels and the importance of DCs to the development and maintenance of asthma. (Clinical trials.gov identifier: NCT00411320)
    Clinical & Experimental Allergy 02/2011; 41(5):665-72. DOI:10.1111/j.1365-2222.2010.03692.x · 4.32 Impact Factor
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    ABSTRACT: Introduction and objectives Idiopathic pulmonary fibrosis (IPF) is common, largely unresponsive to treatment with a median survival of 3 years. New therapies are urgently required. IPF is characterised by proliferation of pulmonary mesenchymal cells through epithelial mesenchymal transition, resident fibroblast proliferation and circulating fibrocyte recruitment. We have previously demonstrated that the potassium channel KCa3.1 regulates lung mesenchymal cell proliferation, is up-regulated by TGFβ, an important driver of IPF, and is present in fibrocytes in peripheral blood. We tested the hypotheses that KCa3.1 is up-regulated in IPF using the bleomycin-induced pulmonary fibrosis murine model and that KCa3.1 inhibition reduces pulmonary fibrosis.
    Thorax 11/2010; 65(Suppl 4):A63-A63. DOI:10.1136/thx.2010.150946.40 · 8.56 Impact Factor