Mechanism of macrophage injury following traumatic hemorrhagic shock: through PTX-sensitive G-protein-mediated signal transduction pathway.
- Author:
Jinghua LIU
1
;
Liangming LIU
;
Huisun CHEN
;
Deyao HU
;
Huaiqiong LIU
Author Information
- Publication Type:Journal Article
- MeSH: Analysis of Variance; Animals; GTP-Binding Proteins; immunology; metabolism; Histocompatibility Antigens Class II; immunology; Immunoblotting; Lipopolysaccharides; pharmacology; Macrophages, Peritoneal; immunology; metabolism; Male; Rats; Rats, Wistar; Shock, Hemorrhagic; blood; immunology; Signal Transduction; Tumor Necrosis Factor-alpha; biosynthesis
- From: Chinese Journal of Traumatology 2002;5(1):46-51
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo study the mechanism of macrophage injury after trauma-hemorrhagic shock.
METHODSWistar 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).
RESULTSThe 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.
CONCLUSIONSPTX-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.