title: Protein kinase C-δ mediates sepsis-induced activation of complement 5a and urokinase-type plasminogen activator signaling in macrophages.
abstract: OBJECTIVE
  Activations of the complement C5a (C5a) and the urokinase-type plasminogen activator (uPA) are commonly seen together during sepsis. However, the mechanism linking these two important pathways remains elusive.
  
  
  METHODS
  We used the C57BL/6 J mice model of sepsis induced by cecal ligation puncture (CLP) procedure, injected anti-C5aR or rottlerin through the tail vein to neutralize C5aR or PKC-δ, and then isolated peritoneal macrophages. Total RNA was isolated from the cells and analyzed by quantitative PCR.
  
  
  RESULTS
  Our study revealed that neutralizing C5aR markedly inhibited sepsis-induced uPA receptor (uPAR) expression and its downstream signaling in macrophage. Similarly, neutralizing uPAR suppressed sepsis activation of C5a signaling. Importantly, inhibition of PKC-δ largely blocked sepsis-induced expression of C5aR and uPAR.
  
  
  CONCLUSIONS
  Our study demonstrates a crosstalk between the complement C5a signaling and the fibrinolytic uPA pathways, which may depend on each other to maintain their expression and signaling, and reveals a central role of PKC-δ in mediating sepsis-induced activation of these pathways.
authors.affiliation: Center for Infection and Immunity Research, School of Life Sciences, Hubei University, Wuhan, 430062, Hubei, People's Republic of China.
authors.forename: Xiao-song
authors.initials: XS
authors.lastname: Yang
authors.forename: Meng-yuan
authors.initials: MY
authors.lastname: Liu
authors.forename: Hai-mou
authors.initials: HM
authors.lastname: Zhang
authors.forename: Bing-zhong
authors.initials: BZ
authors.lastname: Xue
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.forename: Dong-xu
authors.initials: DX
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015936:Complement C5a / Q000235:genetics / Q000276:immunology*; D005260:Female; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D051745:Protein Kinase C-delta / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000276:immunology*
chemical_list: D015936:Complement C5a; D051745:Protein Kinase C-delta; D014568:Urokinase-Type Plasminogen Activator