Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw
Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw
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DOI：
10.1038/sj.bjp.0702634
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发表时间：
1999-07-01
影响因子：
7.3
通讯作者：
Wallace, JL
中科院分区：
文献类型：
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作者：
Vergnolle, N;Hollenberg, MD;Wallace, JL
1在本研究中，我们观察了注射PAR（2）的特异性激动剂（两种PAR（2）活化肽）后大鼠后爪中炎症反应的发展。这种炎症的特征在于水肿和粒细胞浸润。2两种选择性PAR（2）激活肽SLGRL-NH 2和trans-cinnamoyl-LIGRLO-NH 2在足底注射后1- 6小时诱导大鼠后爪显著水肿。注射PAR（2）激活肽后6小时，爪组织显示组织结构完全破坏，沿着炎性细胞浸润。3在发炎的爪中，PAR（2）免疫反应性在内皮细胞和浸润的炎性细胞上表达。用化合物48/80处理，但未通过用肥大细胞稳定剂crologyn预处理大鼠而改变。用环氧合酶抑制剂预处理大鼠（吲哚美辛）或一氧化氮合酶抑制剂（L-N-ω-硝基-L-精氨酸甲酯）对PAR（2）-活化肽诱导的水肿没有影响。5这些结果表明，PAR（2）-活化肽给药到大鼠爪中诱导了以持续水肿为特征的急性炎症反应（至少6小时）和粒细胞浸润。PAR（2）诱导的炎症反应是通过一种机制发生的，这种机制在很大程度上不依赖于肥大细胞的活化，也不依赖于前列腺素类和一氧化氮的产生。
1 In the present study, we have observed the development of an inflammatory reaction in the rat hindpaw, following the injection of specific agonists of PAR(2) (two PAR(2) activating peptides). This inflammation was characterized by oedema and granulocyte infiltration.2 Two selective PAR(2) activating peptides, SLGRL-NH2 and trans-cinnamoyI-LIGRLO-NH2 induced significant oedema in the rat hindpaw from 1-6h following subplantar injection. Six hours after the PAR(2)-activating peptide injection, the paw tissues showed a complete disruption of tissue architecture along with an inflammatory cell infiltrate.3 In the inflamed paw, PAR(2)-immunoreactivity was expressed on endothelial cells as well as on the infiltrating inflammatory cells.4 The oedema induced by the injection of the two PAR(2) activating peptides was slightly reduced in rats pre-treated with compound 48/80, but was not modified by pre-treatment of rats with cromolyn, a mast cell stabilizer. Pre-treatment of rats with a cyclo-oxygenase inhibitor (indomethacin) or a nitric oxide synthase inhibitor (L-N-omega-nitro-L-arginine methyl ester) had no effect on the oedema induced by the PAR(2)-activating peptides.5 These results demonstrate that the administration of PAR(2)-activating peptides into the rat paw induced an acute inflammatory response characterized by a persistent oedema (at least 6 h) and granulocyte infiltration. The PAR(2)-induced inffammatory response occurred through a mechanism largely independent of mast cell activation, and of the production of prostanoids and nitric oxide.