Effect of hemorrhagic shock on endotoxin-induced TNF production and its molecular mechanism in rats.
The present study was designed to investigate the production of tumor necrosis factor alpha (TNF alpha) induced by low-dose (1 microgram/kg) lipopolysaccharide (LPS) and its cellular source after hemorrhagic shock (HS) in rats, and to further analyze the mechanism for increased sensitivity to LPS through looking at expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs and kidneys. It was found in vivo that plasma TNF alpha levels in the HS + LPS group were 20-fold higher than that in the HS group (P < 0.01), and 2.7-fold higher than that in the LPS group (P < 0.05). It was shown in vitro that the capacity of peripheral white blood cells to produce TNF alpha in response to LPS stimulation was significantly decreased by 126% (P < 0.01) and 57% (P < 0.05) compared with pre-shock levels and the sham group respectively at the end of resuscitation following shock, and was still markedly decreased 3 hours after resuscitation, while the capacity of Kupffer cells was significantly increased by 110% compared with the sham group (P < 0.01) after shock and resuscitation. Results from RT-PCR showed that expression of LBP mRNA in the liver, lungs and kidneys was increased after shock and resuscitation. It is suggested that hemorrhagic shock could significantly enhance endotoxin-induced TNF alpha production, which might be due to up-regulation of LBP expression in tissues after shock, and tissue macrophages might be the main source of cytokine production.
Jiang
J
J
Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 630042.
Diao
Y
Y
Tian
K
K
Chen
H
H
Zhu
P
P
Wang
Z
Z
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D007728:Kupffer Cells / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008562:Membrane Glycoproteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein