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Proteinase-activated Receptor 2 Blockade Impairs CCL11- Or Allergen-Induced Eosinophil Recruitment in Experimental Pleurisy

Proteinase-activated Receptor 2 Blockade Impairs CCL11- Or Allergen-Induced Eosinophil Recruitment in Experimental Pleurisy

Natália A Matos, Josiane F Silva, Karine A Damasceno, Geovanni D Cassali, Virginia S Lemos, Igor D G Duarte, André Klein

Eur J Pharmacol. 2014 Oct 5;740:627-33.

PMID: 24972241

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP789488773	ENMD-1068 hydrochloride		789488-77-3 (free base)	Price

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