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Mast cell tryptase induces eosinophil recruitment in the pleural cavity of mice via proteinase-activated receptor 2

机译:肥大细胞类胰蛋白酶通过蛋白酶激活受体2诱导小鼠胸膜腔内嗜酸性粒细胞募集

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摘要

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-NH 2-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.
机译:蛋白酶激活受体(PAR)2已牵涉到嗜酸性粒细胞的迁移。肥大细胞(MC)类胰蛋白酶也通过激活PAR-2参与了过敏性疾病,但该受体在MC类胰蛋白酶诱导的炎症中的作用尚不清楚。这项研究旨在调查MC类胰蛋白酶或PAR-2激活肽(SLIGRL-NH2)诱导嗜酸性粒细胞募集到小鼠胸膜腔的能力。注射肥大细胞类胰蛋白酶的小鼠用PAR-2拮抗剂ENMD-1068预处理。用肥大细胞类胰蛋白酶抑制剂APC 366预处理注射SLIGRL-NH2的小鼠,并在24或48小时后分析嗜酸性粒细胞迁移进入胸膜腔并分析PAR-2的表达。 SLIGRL-NH 2诱导的嗜酸性粒细胞募集被APC 366抑制,而MC类胰蛋白酶诱导的嗜酸性粒细胞募集被ENMD-1068取消。 MC类胰蛋白酶诱导胸膜嗜酸性粒细胞上的PAR-2表达。我们的结果证明了PAR-2在介导小鼠MC类胰蛋白酶引起的胸膜炎中嗜酸性粒细胞募集中起关键作用。 MC类胰蛋白酶在嗜酸性粒细胞上诱导PAR-2表达的能力证实了MC类胰蛋白酶和PAR-2与调节嗜酸性粒细胞迁移的相关性。

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