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Inammation, Vol. 36, No. 6, December 2013 (# 2013) DOI: 10.1007/s10753-013-9664-5
Mast Cell Tryptase Induces Eosinophil Recruitment in the Pleural Cavity of Mice via Proteinase-Activated Receptor 2
Natlia A. Matos,1 Josiane F. Silva,2 Tamires C. Matsui,1 Karine A. Damasceno,3
Igor D. G. Duarte,1 Virginia S. Lemos,2 Geovanni D. Cassali,3 and Andr Klein1,4
AbstractProteinase-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 inammation 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.
KEY WORDS: eosinophils; eosinophil migration; mast cell tryptase; PAR-2; pleurisy.
INTRODUCTION
Eosinophils appear to play an important role in the pathogenesis of allergic diseases. They are typically tissue-dwelling cells, and in allergic disorders, increased numbers of activated eosinophils are observed in the submucosa and mucosa of affected tissues [1]. These cells are considered the effectors of allergic and MC/IgE-mediated reactions, and they are recruited from blood vessels into the allergy-
inamed tissue by the local production of eotaxin-1/CCL11, leukotriene (LT)B4, and IL-5 [14], which are produced by airway epithelial cells, macrophages, eosinophils, and mast cells [57]. Once at the tissue, eosinophils are a crucial source of cationic proteins, lipid mediators, oxygen-derived radicals, cytokines, and chemokines, which play an important role in the pathogenesis and severity of allergic diseases [1, 8]. Thus, understanding the mechanisms underlying eosinophil recruitment in vivo may aid the development of novel strategies for the treatment of allergic diseases.