The Involvement of Kupffer Cells in Carbon Tetrachloride Toxicity

Edwards, Miles J.; Keller, Barbara; Kauffman, F. C.; Thurman, Ronald G.

doi:10.1006/taap.1993.1069

Cited by 243 publications

(146 citation statements)

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“…GdCl 3 is a rare earth metal known to block liver macrophages. 23,24 It has been reported to abrogate hepatic injury induced by a variety of toxicants, including acetaminophen, 25 carbon tetrachloride, 26 galactosamine, 27,28 1,2-dichlorobenzene, 29 and endotoxin, 30,31 suggesting that the toxicity of each of these agents is mediated, in part, by macrophages. Because macrophage-induced tissue injury involves direct contact between parenchymal and infiltrating leukocytes, we examined the effects of GdCl 3 treatment of rats on alterations in cell adhesion molecule expression induced by acute endotoxemia.…”

Section: Effects Of Gdcl 3 Treatment Of Rats On Liver Macrophagesmentioning

confidence: 99%

Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats

et al. 1999

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Cell adhesion molecules are important for localized accumulation of phagocytes at sites of tissue damage. In the present studies, we analyzed the effects of blocking hepatic macrophages on expression of ␤ 2 integrins and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules on liver cells during acute endotoxemia. Flow cytometric analysis revealed distinct subpopulations of macrophages from control animals that varied on the basis of their size and density. In contrast, hepatocytes and endothelial cells were relatively homogeneous. Treatment of rats with endotoxin (5 mg/kg, intravenously) resulted in a time-dependent increase in the percentage of small, dense macrophages and a progressive loss of larger, less-dense cells. In contrast, no major effects were observed on the physical properties of hepatocytes or endothelial cells. ICAM-1 was found to be constitutively expressed on endothelial cells and hepatocytes, as well as on macrophages. Induction of acute endotoxemia resulted in a time-dependent increase in ICAM-1 expression on hepatocytes, which was observed within 3 hours and reached a maximum after 24 hours. An increase in ICAM-1 expression was also observed on endothelial cells and on macrophages at 3 hours, followed by a decrease at 24 to 48 hours. Macrophages and endothelial cells also constitutively expressed ␤ 2 integrins. Induction of acute endotoxemia had no effect on Tissue damage initiates an inflammatory response characterized by an accumulation of macrophages at the site of injury. These cells are primarily derived from blood monocytes. Cell adhesion molecules are a group of membraneassociated proteins present on leukocytes, endothelial cells, and parenchymal cells that facilitate monocyte adherence and emigration out of the blood and into the tissue. Expression of several different classes of cell adhesion molecules have been reported to be up-regulated on liver cells after exposure of animals to hepatotoxic doses of alcohol 1,2 or endotoxin, 3,4 following reperfusion injury, 5,6 and in humans with acute and chronic inflammatory liver diseases. 7-9 Increased quantities of soluble circulating adhesion molecules have also been detected in various models of liver injury. 2,7,8,10 These findings, together with the observation that liver injury is abrogated by administration of antibodies to certain cell adhesion molecules, [4][5][6]11 suggest that they play a role in hepatotoxicity associated with inflammation.Endotoxin is a bacterially derived product known to induce liver injury at toxic doses. 12 We have previously demonstrated that acute endotoxemia is associated with an increase in the number of macrophages in the liver. 13,14 These cells are activated to release reactive oxygen and nitrogen intermediates that we speculate contribute to hepatotoxicity. 14-17 Intercellular adhesion molecule-1 (ICAM-1) is one important cell surface molecule that mediates antigenindependent contact between cells. ICAM-1 serves as a counter-receptor for the ␤ 2 integrins, LFA-1 and MAC-1. [18][19][20] Inter...

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Section: Effects Of Gdcl 3 Treatment Of Rats On Liver Macrophagesmentioning

confidence: 99%

Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats

et al. 1999

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“…33 Acetaldehyde-modified albumin (AA-Alb) was prepared for RME studies by iodinating BSA using the chloramine-T method as de-Twenty-four hours after injection with GdCl 3 , rats were anesthetized, and the clearance and degradation of 125 I-f-Alb were deterscribed above. Albumin was modified under many different reaction conditions to create acetaldehyde-protein adducts that may repremined by in situ isolated perfusion as outlined above.…”

Section: Gadolinium Chloride Treatment To Kill Endogenous Kupffer Cellsmentioning

confidence: 99%

Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells

Thiele¹

1996

Hepatology

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effects of ethanol on liver endothelial cells (LECs). However, Previous reports have shown that long-term ethanolRees et al. 1 have shown recently that the uptake and degradaadministration alters receptor-mediated endocytosis tion of formaldehyde-modified albumin (f-Alb) by the scaven-(RME) of a variety of macromolecules by liver endotheger receptor on LECs is decreased markedly by long-term lial cells (LEC). Acetaldehyde is the major metabolic ethanol consumption. product of ethanol metabolism and has been shown toResearch for the last several years has shown that LECs bind to proteins to form adducts. In this study, the level play an active role in the reticuloendothelial system of the of protein modification by acetaldehyde necessary for liver. Specifically, LECs are involved in clearance from blood the uptake and degradation of acetaldehyde-modified of a variety of substances, including connective tissue compoproteins by LEC was investigated. Bovine serum albunents and several types of modified proteins. 2 In fact, RME min (BSA) acetaldehyde adducts were prepared by incubation of albumin with acetaldehyde at 100 mmol/L for and degradation by LECs are the major mechanisms for 1 hour at 37ЊC, and 1 mmol/L or 0.2 mmol/L for 5 days clearance of circulating hyaluronic acid, denatured collagens, at 37ЊC. In situ liver perfusion in the presence of these the N-terminal propeptide of type III collagen PIIINP, lamiadducts resulted in the degradation of 107 { 10.02 mg, nin, mannosylated glycoproteins, acetylated low-density lipo-69.82 { 5 mg, and 2.5 { 0.42 mg of acetaldehyde-adducted protein (LDL), and f-Alb. Receptors for chemically modified albumin, respectively, during a 4-hour period. These val-proteins, such as acetylated LDL and f-Alb, have been collecues were decreased by 53%, 67%, and nearly 100%, re-tively referred to as scavenger receptors. There has been spectively, in livers from ethanol-fed rats. Additionally, some debate as to whether there is one receptor for acetylated modification of protein with 1 mmol/L of acetaldehyde LDL and f-Alb or whether there is one receptor for each. for different periods of time and/or pH altered the Although macrophages and LECs can clear f-Alb and aceamount of 14 C-acetaldehyde binding, but no signifi-tylated LDL, they are cleared predominantly from the circucant changes in degradation were observed. Finally, lation by LECs. 3,4 Horiuchi et al. have shown that, although an excess of formaldehyde-modified albumin totally acetylated LDL did inhibit binding of f-Alb to sinusoidal endoinhibited the degradation of acetaldehyde adducts, thelial cells, the converse did not occur. 5 Additionally, an suggesting that they use the same receptor. These antibody specific for the f-Alb receptor did not inhibit endocydata show that acetaldehyde-modified proteins may tosis of acetylated LDL. 6 Some investigators maintain that be taken up and degraded by the scavenger receptor there are different receptors for these modified proteins, 7,8 on LEC. This uptake and degradation are dependent ...

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“…For example, experimental acute liver injury with CCl 4 is characterized by centrilobular necrosis resulting from the formation of free radicals and reactive oxygen species during the metabolism of CCl 4 by cytochrome P450 and the activation of Kupffer cells by free radicals (Recknagel and Glende 1973;Edwards et al, 1993). The damage of liver cells accompanies the release of liver function enzymes, such as g-glutamyl transferase (GGT; EC 2.3.2.2), alanine aminotransferase (ALT; EC 2.6.1.1), and aspartate aminotransferase (AST; EC 2.6.1.2) into the blood (Skinner et al, 1984;Shaper et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Intake of purple sweet potato beverage affects on serum hepatic biomarker levels of healthy adult men with borderline hepatitis

Suda

Ishikawa

Hatakeyama³

et al. 2007

Eur J Clin Nutr

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Objective: To examine the effect of purple sweet potato (PSP) beverage rich in acylated anthocyanins on serum hepatic biomarkers in healthy Japanese men. Design: A randomized, double-blind, placebo-controlled, parallel study. Setting: Kumamoto in Japan. Subjects: Healthy adult men (30-60 years) with borderline hepatitis who had one or more of serum g-glutamyl transferase (GGT), aspertate aminotransferase (AST) and alanine aminotransferase (ALT) levels over normal ranges, and who were negative for hepatitis virus were openly recruited by an advertisement. Of the 48 persons enrolled, 38 (mean age 43.0 years (30-54 years)) completed the study. Methods: The subjects were randomly assigned to the PSP group and the placebo group. During the 8-week intervention, the subjects in the PSP group consumed two bottles of the PSP beverage with acylated anthocyanins (200.3 mg anthocyanins per 125 ml per bottle) per day, and the subjects in the placebo group, two bottles of a placebo beverage (1.7 mg anthocyanins per 125 ml per bottle). All of the data measured were analyzed by two-way repeated measures analysis of variance (ANOVA) with groups and times. The data of the hepatic markers were analyzed using the Dunnett multiple comparison among the time points and t-test between groups at the same time point. Two-sided Po0.05 were defined as the level of significance. Results: Serum GGT, AST and ALT levels showed interactions (Po0.05) between the beverage groups and time; the others were not affected. The PSP beverage group showed lower hepatic marker levels than the placebo group during the ingestion period, particularly the GGT level (À14.1 IU/l, 95% Confidence intervel (CI) À25.4 to À2.7, P ¼ 0.017 at 2 weeks; À16.8 IU/l, 95% CI À36.2 to 2.5, P ¼ 0.081 at 4 weeks; À26.7 IU/l, 95% CI À47.6 to À5.7, P ¼ 0.014 at 6 weeks and À27.9 IU/l, 95% CI À49.9 to À5.9; P ¼ 0.014 at 8 weeks). No correlation between alcohol consumption and each hepatic biomarker level before and after the ingestion was observed. Conclusion: The intake of the PSP beverage significantly decreased the serum levels of hepatic biomarkers, particularly the GGT level, in healthy men with borderline hepatitis.

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The Involvement of Kupffer Cells in Carbon Tetrachloride Toxicity

Cited by 243 publications

References 0 publications

Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats

Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats

Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells

Intake of purple sweet potato beverage affects on serum hepatic biomarker levels of healthy adult men with borderline hepatitis

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