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Publications [#168907] of Mark W. Dewhirst

Papers Published

  1. JH Huang, LI Cárdenas-Navia, CC Caldwell, TJ Plumb, CG Radu, PN Rocha, T Wilder, JS Bromberg, BN Cronstein, M Sitkovsky, MW Dewhirst, ML Dustin, Requirements for T lymphocyte migration in explanted lymph nodes., Journal of immunology (Baltimore, Md. : 1950), United States, vol. 178 no. 12 (June, 2007), pp. 7747-55, ISSN 0022-1767
    (last updated on 2009/12/31)

    Abstract:
    Although the requirements for T lymphocyte homing to lymph nodes (LNs) are well studied, much less is known about the requirements for T lymphocyte locomotion within LNs. Imaging of murine T lymphocyte migration in explanted LNs using two-photon laser-scanning fluorescence microscopy provides an opportunity to systematically study these requirements. We have developed a closed system for imaging an intact LN with controlled temperature, oxygenation, and perfusion rate. Naive T lymphocyte locomotion in the deep paracortex of the LN required a perfusion rate of >13 microm/s and a partial pressure of O(2) (pO(2)) of >7.4%. Naive T lymphocyte locomotion in the subcapsular region was 38% slower and had higher turning angles and arrest coefficients than naive T lymphocytes in the deep paracortex. T lymphocyte activation decreased the requirement for pO(2), but also decreased the speed of locomotion in the deep paracortex. Although CCR7(-/-) naive T cells displayed a small reduction in locomotion, systemic treatment with pertussis toxin reduced naive T lymphocyte speed by 59%, indicating a contribution of Galpha(i)-mediated signaling, but involvement of other G protein-coupled receptors besides CCR7. Receptor knockouts or pharmacological inhibition in the adenosine, PG/lipoxygenase, lysophosphatidylcholine, and sphingosine-1-phosphate pathways did not individually alter naive T cell migration. These data implicate pO(2), tissue architecture, and G-protein coupled receptor signaling in regulation of naive T lymphocyte migration in explanted LNs.

    Keywords:
    Adenosine • Animals • Cell Movement* • GTP-Binding Protein alpha Subunits, Gi-Go • Lymph Nodes • Mice • Mice, Knockout • Oxygen • Partial Pressure • Perfusion • Receptor, Adenosine A2A • Receptors, CCR7 • Receptors, Chemokine • T-Lymphocytes • analysis • antagonists & inhibitors • chemistry • genetics • immunology* • metabolism • metabolism*


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