Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Inflammation. 2013 Dec;36(6):1260-7. doi: 10.1007/s10753-013-9664-5.
Proteinase-activated receptor (PAR) 2 has been implicated in eosinophil migration. Mast cell (MC) tryptase has been similarly implicated in allergic diseases through the activation of PAR-2, but the role of this receptor in MC tryptase-induced inflammation is not well elucidated. This study aims to investigate the ability of MC tryptase or PAR-2 activating peptide (SLIGRL-NH2) to induce eosinophil recruitment to the pleural cavity of mice. Mast cell tryptase-injected mice were pretreated with PAR-2 antagonist ENMD-1068. Mice injected with SLIGRL-NH2 were pretreated with mast cell tryptase inhibitor APC 366, and eosinophil migration into the pleural cavity and PAR-2 expression was analyzed after 24 or 48 h. SLIGRL-NH2-induced eosinophil recruitment was inhibited by APC 366, and MC tryptase-induced eosinophil recruitment was abolished by ENMD-1068. MC tryptase induced PAR-2 expression on pleural eosinophils. Our results demonstrate a key role for PAR-2 in mediating eosinophil recruitment in MC tryptase-induced pleurisy in mice. The ability of MC tryptase to inducing PAR-2 expression on eosinophils corroborates the relevance of MC tryptase and PAR-2 on modulating eosinophil migration.
蛋白酶激活受体 (PAR) 2 已被牵连到嗜酸性粒细胞迁移中。肥大细胞 (MC) 胰蛋白酶也通过激活 PAR-2 被牵连到过敏疾病中，但该受体在 MC 胰蛋白酶诱导的炎症中的作用尚未得到很好的阐明。本研究旨在探讨 MC 胰蛋白酶或 PAR-2 激活肽 (SLIGRL-NH2) 诱导嗜酸性粒细胞募集到小鼠胸腔的能力。MC 胰蛋白酶注射的小鼠预先用 PAR-2 拮抗剂 ENMD-1068 处理。用肥大细胞胰蛋白酶抑制剂 APC 366 预处理注射 SLIGRL-NH2 的小鼠，并在 24 或 48 小时后分析胸腔内嗜酸性粒细胞迁移和 PAR-2 表达。APC 366 抑制了 SLIGRL-NH2 诱导的嗜酸性粒细胞募集，而 ENMD-1068 则消除了 MC 胰蛋白酶诱导的嗜酸性粒细胞募集。MC 胰蛋白酶诱导胸腔嗜酸性粒细胞表达 PAR-2。我们的结果表明 PAR-2 在介导 MC 胰蛋白酶诱导的小鼠胸腔炎中的嗜酸性粒细胞募集中起着关键作用。MC 胰蛋白酶诱导嗜酸性粒细胞表达 PAR-2 的能力证实了 MC 胰蛋白酶和 PAR-2 在调节嗜酸性粒细胞迁移中的相关性。
