Matos Natália A, Silva Josiane F, Damasceno Karine A, Cassali Geovanni D, Lemos Virginia S, Duarte Igor D G, Klein André
Department of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627 Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Eur J Pharmacol. 2014 Oct 5;740:627-33. doi: 10.1016/j.ejphar.2014.06.018. Epub 2014 Jun 24.
Although proteinase-activated receptor (PAR)-2 has been implicated in inflammatory diseases, its role in regulating eosinophil recruitment in response to chemoattractants remains unclear. Here, we investigated the role of PAR-2 and PAR-2-activating Mast Cell (MC) tryptase on chemokine C-C motif ligand (CCL)11- and antigen-induced eosinophil recruitment to the pleural cavity of BALB/c mice. The PAR-2-activating peptide H-Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL-NH2) induced eosinophil recruitment whereas PAR-2 blockade inhibited ovalbumin (OVA)- or CCL11-induced eosinophil recruitment. Moreover, OVA and CCL11 induced PAR-2 expression in pleural leukocytes, and the MC tryptase inhibitor APC 366 ([N-(1-hydroxy-2-napthoyl)-l-arginyl-l-prolinamide hydrochloride]) abolished CCL11-induced eosinophil recruitment. These results suggest a pro inflammatory effect of PAR-2 and support a role for MC tryptase mediating eosinophil migration via PAR-2 signaling. Taken together, our results suggest that PAR-2 activation through endogenous MC tryptase activity could be required, at least partially, to mediate CCL11-induced eosinophil migration.
尽管蛋白酶激活受体（PAR）-2与炎症性疾病有关，但其在调节嗜酸性粒细胞对趋化因子的募集反应中的作用仍不清楚。在此，我们研究了PAR-2和激活PAR-2的肥大细胞（MC）类胰蛋白酶在趋化因子C-C基序配体（CCL）11和抗原诱导的嗜酸性粒细胞募集到BALB/c小鼠胸腔中的作用。激活PAR-2的肽H-Ser-Leu-Ile-Gly-Arg-Leu-NH2（SLIGRL-NH2）诱导嗜酸性粒细胞募集，而PAR-2阻断则抑制卵清蛋白（OVA）或CCL11诱导的嗜酸性粒细胞募集。此外，OVA和CCL11诱导胸膜白细胞中PAR-2表达，并且MC类胰蛋白酶抑制剂APC 366（[N-（1-羟基-2-萘甲酰基）-L-精氨酰-L-脯氨酰胺盐酸盐]）消除了CCL11诱导的嗜酸性粒细胞募集。这些结果提示PAR-2具有促炎作用，并支持MC类胰蛋白酶通过PAR-2信号传导介导嗜酸性粒细胞迁移的作用。综上所述，我们的结果表明，通过内源性MC类胰蛋白酶活性激活PAR-2可能至少部分是介导CCL11诱导的嗜酸性粒细胞迁移所必需的。
