The Kupffer Cell Inhibition Exacerbates but Splenectomy Prevents Mortality in a Rat Septic Peritonitis Model

Kono, Hiroshi; Fujii, Hideki; Ogiku, Masahito; Hara, Michio; Tsuchiya, Mai; Ishii, Kenichi; Hosomura, Naohiro

doi:10.1016/j.jss.2011.02.031

Cited by 11 publications

(11 citation statements)

References 41 publications

(49 reference statements)

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“…Macrophages and Th1 cell involvement has already been described in several stages of the process of atherosclerotic lesion development, from endothelial dysfunction to plaque rupture [28,29]. The spleen hosts 25% of all lymphocytes of the body, and fulfills an important role in the homeostasis of the immune system, promoting cellular homing, activation and proliferation of lymphocytes and macrophages [16,17,30]. In addition, splenic tissue hosts the largest pool of B cells and plays an important role in B cell maturation [16].…”

Section: Discussionmentioning

confidence: 99%

Splenectomy Increases Atherosclerotic Lesions in Apolipoprotein E Deficient Mice

Rezende

Neto

Fernandes

et al. 2011

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Splenectomy Increases Atherosclerotic Lesions in Apolipoprotein E Deficient Mice

Rezende

Neto

Fernandes

et al. 2011

Journal of Surgical Research

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“…Animals received intravenous administration of 1 ml of lipo-MDP to eliminate the Kupffer cell 72 h before warm ischemia because intravenous injection of 1 ml of lipo-MDP eliminated the Kupffer cell but not the splenic macrophage (Boulton et al, 1998;Kono et al, 2011). Nonentrapped liposome (lipo; 1 ml/animal) was administered as a control.…”

Section: Methodsmentioning

confidence: 99%

Glycyrrhizin Prevents Liver Injury by Inhibition of High-Mobility Group Box 1 Production by Kupffer Cells after Ischemia-Reperfusion in Rats

Ogiku

Kono²,

Hara³

et al. 2011

J Pharmacol Exp Ther

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High-mobility group box 1 (HMGB1) acts as an early mediator of inflammation and organ damage in hepatic ischemia-reperfusion (I/R) injury. Glycyrrhizin is a natural anti-inflammatory and antiviral triterpene in clinical use. The purpose of this study was to investigate the effect of glycyrrhizin on liver injury caused by I/R and production of HMGB1 by Kupffer cells in rats. In the first test period, rats were given saline or glycyrrhizin 20 min before segmental hepatic warm I/R. Serum alanine aminotransferase and HMGB1 levels and hepatic histopathological findings were evaluated after I/R. Furthermore, expression of HMGB1 in the liver was assessed by immunohistochemical staining after I/R. Kupffer cells were isolated by collagenase digestion and differential centrifugation, and production of HMGB1 was assessed. In another set of experiments, the effect of inhibition of Kupffer cells by injection of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP) on liver injury and expression of HMGB1 were investigated after I/R. Liver injury was prevented in the glycyrrhizin group compared with the control group. Furthermore, serum HMGB1 levels were also significantly blunted in the glycyrrhizin group compared with the control group. Cells expressing HMGB1 were detected in the hepatic sinusoid by immunohistochemistry and recognized morphologically as Kupffer cells. Furthermore, the expression of HMGB1 was reduced in the glycyrrhizin group compared with the control group. Production of HMGB1 was reduced in Kupffer cells isolated from the glycyrrhizin group compared with the control group. It is noteworthy that treatment with lipo-MDP significantly blunted serum HMGB1 levels and prevented liver injury after I/R. These results suggest that glycyrrhizin has the therapeutic potential to prevent warm I/R-induced injury during hepato-biliary surgery.

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“…13 Recent studies have shown that splenectomized animals that undergo cecal ligation and incision (CLI) have improved survival compared with their intact counterparts. 14,15 Spleens harbor inflammatory cells such as T and B cells, monocytes and neutrophils. When the body detects a bacterial load in the bloodstream, the spleen is stimulated and plays a key role in clearance of bacteremia.…”

Section: Introductionmentioning

confidence: 99%

Effect of hypothermia on splenic leukocyte modulation and survival duration in severely septic rats

Willis

Charles

Guidry

et al. 2017

Journal of Surgical Research

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Background Therapeutic hypothermia in severe septic shock is associated with prolonged survival. We hypothesized that moderate hypothermia would prolong survival and modulate the inflammatory response in rats with septic shock by exerting its therapeutic effect on splenic leukocytes. Materials and Methods Severe septic shock was created in rats by cecal ligation and incision (CLI). One hour after CLI or laparotomy, rats were randomized to sham, normothermia (NT), or 4 hours of hypothermia (HT) followed by 2 hours of rewarming. Hypothermia (3l±1°C) was induced using a cooling blanket, and monitored via a rectal temperature probe. Results Survival duration was 2.78±1.0 hours in NT rats and 8.33±0.32 hours in HT rats (n=8/group, p<0.0001). In separate groups, three hours after CLI, the spleen weight was significantly smaller in NT rats (769±100 mg) than in HT rats (947±157 mg, p=0.04). Fluorescent immunostaining of formyl peptide receptors (FPR) on leukocytes in spleen tissue showed considerably higher FPR expression in HT rats than in NT rats. Significantly elevated pro-inflammatory cytokines and myeloperoxidase (MPO) enzyme in plasma were found in NT rats compared with HT rats. Anti-inflammatory cytokine, IL-10, was significantly higher in HT rats. Both pro-inflammatory cytokines and plasma MPO were significantly reduced in splenectomized NT rats. Conclusions Moderate hypothermic therapy significantly prolongs the survival duration of rats with severe septic shock. Hypothermia dampens the inflammatory response during septic shock by modulating the spleen to an anti-inflammatory mode and preventing the spleen from releasing activated splenic leukocytes into the blood.

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The Kupffer Cell Inhibition Exacerbates but Splenectomy Prevents Mortality in a Rat Septic Peritonitis Model

Cited by 11 publications

References 41 publications

Splenectomy Increases Atherosclerotic Lesions in Apolipoprotein E Deficient Mice

Splenectomy Increases Atherosclerotic Lesions in Apolipoprotein E Deficient Mice

Glycyrrhizin Prevents Liver Injury by Inhibition of High-Mobility Group Box 1 Production by Kupffer Cells after Ischemia-Reperfusion in Rats

Effect of hypothermia on splenic leukocyte modulation and survival duration in severely septic rats

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