title: Proteinase-activated receptor 2 blockade impairs CCL11- or allergen-induced eosinophil recruitment in experimental pleurisy.
abstract: 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.
authors: Department of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627 Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
authors: Natália A
authors: NA
authors: Matos
authors: Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Josiane F
authors: JF
authors: Silva
authors: Department of General Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Karine A
authors: KA
authors: Damasceno
authors: Department of General Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Geovanni D
authors: GD
authors: Cassali
authors: Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Virginia S
authors: VS
authors: Lemos
authors: Department of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627 Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
authors: Igor D G
authors: ID
authors: Duarte
authors: Department of Pharmacology, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627 Pampulha, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: klein@ufmg.br.
authors: André
authors: A
authors: Klein
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D054413:Chemokine CCL11 / Q000276:immunology*; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D005260:Female; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010879:Piperazines / Q000494:pharmacology; D010998:Pleurisy / Q000276:immunology*; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D053802:Tryptases / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: C518710:1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine; D000485:Allergens; D054413:Chemokine CCL11; D004151:Dipeptides; C094700:N-(1-hydroxy-2-naphthoyl)arginyl-prolinamide; D009842:Oligopeptides; D010879:Piperazines; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D010047:Ovalbumin; D053802:Tryptases
keywords: CCL11; Eosinophil; Eosinophil migration; PAR-2; Proteinase-activated receptor-2