Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 591-599 |
| Number of pages | 8 |
| Journal | British Journal of Pharmacology |
| Volume | 149 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2006 |
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Keywords
- cell trafficking
- inflammation
- knockout mice
- T cells
- B cells
- protease-activated receptor
- reactive oxygen species
- pharmacology
- biomedical sciences
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Activation of mouse protease-activated receptor-2 induces lymphocyte adhesion and generation of reactive oxygen species. / Kane, K.A.; Lim, S.Y.; Tennant, G.M.; Kennedy, S.; Wainwright, C.L.
In: British Journal of Pharmacology, Vol. 149, No. 5, 2006, p. 591-599.Research output: Contribution to journal › Article
TY - JOUR
T1 - Activation of mouse protease-activated receptor-2 induces lymphocyte adhesion and generation of reactive oxygen species
AU - Kane, K.A.
AU - Lim, S.Y.
AU - Tennant, G.M.
AU - Kennedy, S.
AU - Wainwright, C.L.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - cell trafficking
KW - inflammation
KW - knockout mice
KW - T cells
KW - B cells
KW - protease-activated receptor
KW - reactive oxygen species
KW - pharmacology
KW - biomedical sciences
UR - http://dx.doi.org/10.1038/sj.bjp.0706905
U2 - 10.1038/sj.bjp.0706905
DO - 10.1038/sj.bjp.0706905
M3 - Article
VL - 149
SP - 591
EP - 599
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 5
ER -