title: Mechanism of macrophage injury following traumatic hemorrhagic shock: through PTX-sensitive G-protein-mediated signal transduction pathway.
abstract: OBJECTIVE
  To study the mechanism of macrophage injury after trauma-hemorrhagic shock.
  
  
  METHODS
  Wistar male rats underwent trauma (closed bone fracture) and hemorrhage (mean arterial blood pressure of 35 mm Hg+/-5 mm Hg for 60 minutes, following fluid resuscitation). Rats without trauma, hemorrhage or fluid resuscitation served as controls. Peritoneal macrophages were harvested at 6 hours and 1, 2, 3, 7 days after traumatic hemorrhagic shock to determine the effects of pertussis toxin (PTX, as a specific inhibitor to Gi(alpha) and cholera toxin (CTX, as a stimulant to Gs(alpha) on macrophage-Ia expression and TNF-alpha production and levels of Gi(alpha) and Gs(alpha).
  
  
  RESULTS
  The macrophages from the injured rats revealed a significant decrease of Ia positive number and TNF-alpha release in response to LPS. Wi th pretreatment with PTX 10-100 ng/ml Ia positive cells and LPS-induced TNFalpha production in both control and impaired macrophages populations were dos e dependently increased. Both macrophages populations were not responding to CTX treatment (10-100 ng/ml). Western blot analyses showed that the levels of Gi(alpha) protein expression increased as much as 116.5%-148.8% of the control level fro m 6 hours through 7 days after traumatic hemorrhage. The levels of Gs protein expression were reduced at 6 hours and decreased to the lowest degree; 36% o f the control at day 1, began to return at day 2 and returned to the normal level at day 7, following traumatic hemorrhagic shock.
  
  
  CONCLUSIONS
  PTX-sensitive G-protein may participate in th e modulation of macrophage-Ia expression and TNF-alpha release following traumatic hemorrhagic shock. Analyses of the alteration of Gi(alpha) and Gs protein express ions further supports the concept that G-protein is involved in trauma-induced macrophage signal transduction pathways.
authors.affiliation: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Liu
authors.forename: Liangming
authors.initials: L
authors.lastname: Liu
authors.forename: Huisun
authors.initials: H
authors.lastname: Chen
authors.forename: Deyao
authors.initials: D
authors.lastname: Hu
authors.forename: Huaiqiong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019204:GTP-Binding Proteins