Blockade of Proteinase-Activated Receptor-4 Inhibits the Eosinophil Recruitment Induced by Eotaxin-1 in the Pleural Cavity of Mice

Objective and Design: Although proteinase-activated receptor (PAR)-4 has been implicated in inflammation, its role in regulating eosinophil recruitment in response to chemoattractants has not yet been demonstrated. To investigate the contribution of proteinases and PAR-4 activation to eosinophil migration in response to eotaxin-1 or leukotriene B-4 (LTB4), the effects of aprotinin or PAR-4 antagonist transcinnamoyl-YPGKF-NH2 (tcY-NH2) on eosinophil migration induced by these chemoattractants were investigated. Methods: BALB/c mice were pretreated with aprotinin or tcY-NH2 (30 mu g/mouse) prior to intrapleural injection of LTB4 or eotaxin-1 and the number of infiltrating eosinophils was determined 48 h later. Results: Aprotinin (1 mg/kg) inhibited eosinophil recruitment induced by eotaxin-1 (p < 0.01), but not that induced by LTB4. Moreover, tcY-NH2 treatment inhibited eosinophil recruitment in response to eotaxin-1 (p < 0.01 by ANOVA/Tukey post-test). Conclusion: These data suggest that aprotinin-inhibited proteinases participate in eosinophil migration induced by eotaxin-1 and that PAR-4 activation plays an important role in regulating this migration. Copyright (C) 2010 S. Karger AG, Basel