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

Abstract

Background and Purpose: 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-2À/À) mice. Experimental Approach: Lymphocyte adhesion to the luminal surface of mouse isolated aortae was measured using 51 Crlabelled leukocytes and ROS generation from isolated lymphocytes was quantified using chemiluminescence. Key results: 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-2À/À mice indicating a PAR-2 dependent mechanism. Superoxide dismutase had a greater inhibitory effect in PAR-2À/À mice compared to wild type mice when lymphocytes were stimulated with PMA but not trypsin. Conclusions and Implications: 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.

Protease-Activated Receptor 2 Deficiency Reduces Cardiac Ischemia/Reperfusion Injury

“…The reduction of nitrotyrosine levels in the myocardium of PAR-2 deficient mice suggests that oxidative/nitrative stress is one of the mechanisms by which PAR-2 may enhances MI. This concept is supported by recent publications indicating that activation of PAR-2 leads to generation of both nitric oxide and ROS, including superoxide anion19, 33, 34.…”

Protease-activated receptor-2 activation: a major actor in intestinal inflammation

“…It is important to point out that our study does not necessarily imply that PAR 2 activation, T cells and Th cytokines are unrelated. Indeed, PAR 2 is expressed on T cells and may play a significant role in priming T helper cell response by inducing dendritic cell maturation, as well as regulating lymphocyte adhesion and generating reactive oxygen species 16 17. A number of pieces of in vitro and in vivo evidence also indicate that PAR 2 agonists can induce the release of pro-inflammatory cytokines from various cell types 3 7.…”

Antisense Oligodeoxynucleotide Against Tissue Factor Inhibits Human Umbilical Vein Endothelial Cells Injury Induced by Anoxia-Reoxygenation

“…TF binds to trace FVIIa and forms TF-FVIIa complex, which irritates phospholipase C-dependent calcium transients and subsequent generation of ROS, the presence of the cytoplasmic tail of TF is essential for TF-FVIIa complex driven phospholipase C-dependent generation of ROS [32]. Moreover, TF also contributes to ROS generation by activation of PAR-2 [33].…”