Mast Cell Tryptase Induces Eosinophil Recruitment in the Pleural Cavity of Mice via Proteinase-Activated Receptor 2

Abstract

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-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.

Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

“…Although the mechanisms of tryptase-induced transmigration of eosinophils are not completely understood, some experimental studies leave no doubt about the involvement of tryptase in such processes. Decreased eosinophil recruitment to tissues is observed in mast cell-deficient mice (de Boer et al 2014), as well as in experimental models where the PAR2 receptor was blocked (Hyun et al 2008;Matos et al 2013). Moreover, the positive correlation observed in this study between numbers of tryptase-IR mast cells and eosinophils could be also interpreted as evidence for the role of tryptase in eosinophil survival.…”

“…In other models, such as allergic lung diseases, the participation of tryptase in eosinophil tissue infiltration has already been reported (Schmidlin et al 2002;Bolton et al 2003;Vliagoftis et al 2004;Matos et al 2013). Although the mechanisms of tryptase-induced transmigration of eosinophils are not completely understood, some experimental studies leave no doubt about the involvement of tryptase in such processes.…”

“…After interaction with tryptase, PAR2 is activated upon cleavage of its N-terminus, followed by its internalization and its targeting into lysosomes (Ramachandran et al 2012). There is now convincing evidence for a role for tryptase in eosinophil activation, through its linkage to PAR2 (Matos et al 2013), leading to cellular release of leukotrienes and reactive oxygen species formation (Bolton et al 2003). The role of tryptase on eosinophil trafficking appears to be mediated by its ability to interact with endothelial cells and promote selectin-mediated eosinophil adhesion during inflammation (Steinhoff et al 2000;Itoh et al 2005).…”

Proteinase-activated receptor 2 blockade impairs CCL11- or allergen-induced eosinophil recruitment in experimental pleurisy

“…Given that CCL11 induced eosinophil recruitment into the pleural cavity of mice via PAR-2 in our experiments, that the i.pl. injection of OVA in sensitized mice effectively induced eosinophil recruitment, and that MC tryptase mediates eosinophil recruitment into the pleural cavity of mice (Matos et al, 2013) and is a PAR-2-activating proteinase released at allergic sites (Pejler et al, 2007), we decided to investigate the contribution of MC tryptase activity to CCL11-induced eosinophil recruitment through the use of the irreversible MC tryptase inhibitor APC 366.…”

“…PARs family comprises four receptors (PAR-1 to 4), whose activation has been implicated in the regulation of inflammation, including vascular endothelial cell activity, in vivo leukocyte recruitment (Hollenberg and Compton, 2002;Vergnolle et al 2002;Braga et al, 2010;Gomides et al, 2012) and cytokine release (Asokananthan et al, 2002;Steinhoff et al, 2005). PAR-2 is the receptor for trypsin and mast cell (MC) tryptase (Macfarlane et al 2001;Adams et al, 2011) and it is of particular interest because it has been implicated in eosinophil activation (Bolton et al 2003) and in vivo eosinophil and neutrophil migration (Schmidlin et al, 2002;Matos et al, 2013).…”