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Activation of mouse protease-activated receptor-2 induces lymphocyte adhesion and generation of reactive oxygen species

Kane, K.A. and Lim, S.Y. and Tennant, G.M. and Kennedy, S. and Wainwright, C.L. (2006) Activation of mouse protease-activated receptor-2 induces lymphocyte adhesion and generation of reactive oxygen species. British Journal of Pharmacology, 149 (5). pp. 591-599. ISSN 0007-1188

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Abstract

Protease-activated receptor-2 (PAR-2) is expressed on lymphocytes and endothelial cells, and plays a significant role in inflammatory reactions. Since leukocyte-endothelial cell interaction and reactive oxygen species (ROS) generation are hallmarks of the development of inflammation, the effects of PAR-2 activation by trypsin on lymphocyte adhesion and ROS generation was examined utilising PAR-2 wild type and knockout (PAR-2−/−) mice. Trypsin induced adhesion of lymphocytes when added exogenously to the endothelial surface of the aorta for 30 min. Similarly, increased lymphocyte adhesion was also observed when mice were injected with trypsin intravenously 24 h prior to the adhesion assay, an effect which was partly ICAM-1 mediated. Trypsin also increased ROS generation from isolated mouse lymphocytes in a dose-dependent manner. The increase in lymphocyte adhesion and ROS production in response to trypsin were abolished in PAR-2−/− mice indicating a PAR-2 dependent mechanism. Superoxide dismutase had a greater inhibitory effect in PAR-2−/− mice compared to wild type mice when lymphocytes were stimulated with PMA but not trypsin. The present study indicates that activation of PAR-2 may be an important factor in modulating lymphocyte adhesion and ROS generation. The results have implications for developing anti-inflammatory strategies.

Item type: Article
ID code: 7569
Keywords: cell trafficking, inflammation, knockout mice, T cells, B cells, protease-activated receptor, reactive oxygen species, pharmacology, biomedical sciences, Pharmacy and materia medica
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences > Physiology and Pharmacology
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    Depositing user: Strathprints Administrator
    Date Deposited: 14 Apr 2009 10:42
    Last modified: 16 Jul 2013 20:38
    URI: http://strathprints.strath.ac.uk/id/eprint/7569

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