Blockade of proteinase-activated receptor-4 inhibits the eosinophil recruitment induced by eotaxin-1 in the pleural cavity of mice.
OBJECTIVE
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) (LTB(4)), the effects of aprotinin or PAR-4 antagonist trans-cinnamoyl-YPGKF-NH(2) (tcY-NH(2)) on eosinophil migration induced by these chemoattractants were investigated.


METHODS
BALB/c mice were pretreated with aprotinin or tcY-NH(2) (30 μg/mouse) prior to intrapleural injection of LTB(4) 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 LTB(4). Moreover, tcY-NH(2) treatment inhibited eosinophil recruitment in response to eotaxin-1 (p < 0.01 by ANOVA/Tukey post-test).


CONCLUSIONS
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.
Braga
A D
AD
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
Miranda
J P
JP
Ferreira
G M
GM
Bilheiro
R P
RP
Duarte
I D
ID
Francischi
J N
JN
Klein
A
A
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D002465:Cell Movement; D054413:Chemokine CCL11 / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D035422:Pleural Cavity / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010998:Pleurisy / Q000276:immunology; D044462:Receptors, Proteinase-Activated / Q000378:metabolism*
D054413:Chemokine CCL11; D002934:Cinnamates; D009842:Oligopeptides; D044462:Receptors, Proteinase-Activated; C481942:protease-activated receptor 4, mouse; D007975:Leukotriene B4; D010047:Ovalbumin; D007611:Aprotinin