title: Proteinase-activated receptor-4 plays a major role in the recruitment of neutrophils induced by trypsin or carrageenan during pleurisy in mice.
abstract: OBJECTIVE
  The activation of proteinase-activated receptors (PARs) has been implicated in the development of important hallmarks of inflammation, including in vivo leukocyte recruitment. Here, we examined the effects of aprotinin, a potent inhibitor of trypsin proteinase and the kallikrein-kinin system, and the PAR-4 antagonist YPGKF-NH(2) (tcY-NH(2)) on neutrophil recruitment in response to carrageenan and trypsin in the pleural cavity of mice.
  
  
  METHODS
  BALB/c mice were intrapleurally injected with trypsin or PAR-4-activating peptide AY-NH(2), pretreated with aprotinin or tcY-NH(2) (1 μg/cavity) prior to an intrapleural injection of trypsin or carrageenan, or pretreated with leukotriene B(4) antagonist U-75302 (3 μg/cavity) prior to a trypsin injection. The number of infiltrating neutrophils was evaluated after 4 h.
  
  
  RESULTS
  PAR-4-activating peptide AY-NH(2) and trypsin-induced neutrophil recruitment was inhibited by aprotinin, tcY-NH(2) or U-75302. Aprotinin and tcY-NH(2) also inhibited neutrophil recruitment induced by carrageenan.
  
  
  CONCLUSIONS
  These data suggest a key role for PAR-4 in mediating neutrophil recruitment in a mouse model of pleurisy induced by the activity of trypsin or trypsin-like enzymes.
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: L F
authors.initials: LF
authors.lastname: Gomides
authors.forename: I D
authors.initials: ID
authors.lastname: Duarte
authors.forename: R G
authors.initials: RG
authors.lastname: Ferreira
authors.forename: A C
authors.initials: AC
authors.lastname: Perez
authors.forename: J N
authors.initials: JN
authors.lastname: Francischi
authors.forename: A
authors.initials: A
authors.lastname: Klein
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D002351:Carrageenan; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010998:Pleurisy / Q000139:chemically induced / Q000276:immunology*; D044462:Receptors, Proteinase-Activated / Q000037:antagonists & inhibitors / Q000276:immunology*; D014357:Trypsin; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; D044462:Receptors, Proteinase-Activated; D014361:Trypsin Inhibitors; C481942:protease-activated receptor 4, mouse; D002351:Carrageenan; D007611:Aprotinin; D014357:Trypsin