Adaptive Kupffer cell alterations after femur fracture trauma in rats

1997 ◽  
Vol 272 (6) ◽  
pp. G1457-G1462
Author(s):  
T. Huynh ◽  
C. C. Baker ◽  
L. W. Bracey ◽  
J. J. Lemasters
Keyword(s):  
Oxygen Consumption ◽  
Kupffer Cell ◽  
Kupffer Cells ◽  
Cell Function ◽  
Femur Fracture ◽  
Tissue Injury ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Hepatic Oxygen Consumption ◽  
Cell Alterations

Because Kupffer cells constitute the largest fixed macrophage population and reside at a strategic position in hepatic sinusoids, interacting with hepatocytes, circulating cells, and mediators from the gut, they may be important in the inflammatory response after injury. This study examined the effect of remote tissue injury on Kupffer cell function. Femurs of Sprague-Dawley rats were fractured under anesthesia. Subsequently, their livers were perfused for measurement of oxygen consumption and the isolation and culture of Kupffer cells. At 2 and 48 h after femur fracture, hepatic oxygen consumption increased 17 and 19%, respectively. Gadolinium chloride pretreatment to ablate Kupffer cells blocked this increase of hepatic oxygen consumption after femur fracture but had no effect in sham-operated animals. In Kupffer cells isolated and cultured 2 h after femur fracture, superoxide formation stimulated by phorbol ester increased eightfold, phagocytosis increased fourfold, and lipopolysaccharide (LPS)-stimulated prostaglandin E2 increased sixfold in comparison to sham-operated controls. In contrast, LPS-stimulated tumor necrosis factor-alpha and nitric oxide production decreased 50 and 60%, respectively. These data show that peripheral trauma rapidly induces changes in hepatic macrophages characterized by adaptation to a more antimicrobial and less proinflammatory phenotype.

Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1076-G1082 ◽  
Author(s):  
Peter Schemmer ◽  
Nobuyuki Enomoto ◽  
Blair U. Bradford ◽  
Hartwig Bunzendahl ◽  
James A. Raleigh ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Kupffer Cells ◽  
Cell Function ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Hypermetabolic State ◽  
Hypoxia Marker ◽  
Factor Α ◽  
Necrosis Factor

Harvesting trauma to the graft dramatically decreases survival after liver transplantation. Since activated Kupffer cells play a role in primary nonfunction, the purpose of this study was to test the hypothesis that organ manipulation activates Kupffer cells. To mimic what occurs with donor hepatectomy, livers from Sprague-Dawley rats underwent dissection with or without gentle organ manipulation in a standardized manner in situ. Perfused livers exhibited normal values for O2 uptake (105 ± 5 μmol · g−1 · h−1) measured polarigraphically; however, 2 h after organ manipulation, values increased significantly to 160 ± 8 μmol · g−1 · h−1 and binding of pimonidazole, a hypoxia marker, increased about threefold ( P < 0.05). Moreover, Kupffer cells from manipulated livers produced three- to fourfold more tumor necrosis factor-α and PGE2, whereas intracellular calcium concentration increased twofold after lipopolysaccharide compared with unmanipulated controls ( P < 0.05). Gadolinium chloride and glycine prevented both activation of Kupffer cells and effects of organ manipulation. Furthermore, indomethacin given 1 h before manipulation prevented the hypermetabolic state, hypoxia, depletion of glycogen, and release of PGE2 from Kupffer cells. These data indicate that gentle organ manipulation during surgery activates Kupffer cells, leading to metabolic changes dependent on PGE2 from Kupffer cells, which most likely impairs liver function. Thus modulation of Kupffer cell function before organ harvest could be beneficial in human liver transplantation and surgery.

A diet containing glycine improves survival in endotoxin shock in the rat

1996 ◽  
Vol 271 (1) ◽  
pp. G97-G103 ◽  
Author(s):  
K. Ikejima ◽  
Y. Iimuro ◽  
D. T. Forman ◽  
R. G. Thurman
Keyword(s):  
Intravenous Injection ◽  
Kupffer Cells ◽  
Ischemia Reperfusion ◽  
Control Diet ◽  
Hepatic Necrosis ◽  
Endotoxin Shock ◽  
Sprague Dawley ◽  
Hepatic Ischemia ◽  
Necrosis Factor Alpha

In this study, we investigated the effects of a glycine-containing diet (5%) on mortality and liver injury due to intravenous injection of endotoxin [Escherichia coli lipopolysaccharide (LPS)] in Sprague-Dawley rats in vivo. Fifty percent of the rats fed control diet died within 24 h after an intravenous injection of LPS (10 mg/kg), whereas feeding the rats glycine totally prevented mortality and markedly reduced an LPS-induced elevation of serum transaminase levels, hepatic necrosis, and lung injury. The elevation in serum tumor necrosis factor-alpha (TNF-alpha) due to LPS was also blunted and delayed significantly by glycine feeding. In a two-hit model (hepatic ischemia-reperfusion and injection of sublethal LPS), all rats fed control diet died, whereas 83% of glycine-fed animals survived with a significant reduction in transaminases and improved liver and lung histology. LPS elevated intracellular Ca2+ concentration ([Ca2+]i) in cultured Kupffer cells, an effect blocked almost completely by glycine. Glycine most likely reduces injury and mortality by preventing the LPS-induced elevation of [Ca2+]i in Kupffer cells, thereby minimizing toxic eicosanoid and cytokine production.

Kupffer cell-initiated remote hepatic injury following bilateral hindlimb ischemia is complement dependent

2001 ◽  
Vol 280 (2) ◽  
pp. G279-G284 ◽  
Author(s):  
Robert W. Brock ◽  
Robert G. Nie ◽  
Kenneth A. Harris ◽  
Richard F. Potter
Keyword(s):  
Kupffer Cell ◽  
Kupffer Cells ◽  
Hepatic Injury ◽  
Cell Function ◽  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Hindlimb Ischemia ◽  
Male Wistar Rats ◽  
Stimulation Of

Intravital fluorescence microscopy was applied to the livers of male Wistar rats to test the hypothesis that complement mobilization stimulates Kupffer cells and subsequently initiates hepatic injury after hindlimb ischemia/reperfusion (I/R). Following 3 h of limb reperfusion, hepatocellular viability (serum levels of alanine transaminase and cell death via propidium iodide labeling) decreased significantly from levels in sham-operated animals. Inhibition of complement mobilization with soluble complement receptor type 1 (20 mg/kg body wt) and interruption of Kupffer cell function with GdCl3 (1 mg/100g body wt) resulted in significant hepatocellular protection. Although the effects of hindlimb I/R on hepatic microvascular perfusion were manifest as increased heterogeneity, both complement inhibition and suppression of Kupffer cell function resulted in marked improvements. No additional hepatocellular protection and microvascular improvements were provided by combining the interventions. Furthermore, inhibition of complement mobilization significantly depressed Kupffer cell phagocytosis by 42% following limb reperfusion. These results suggest that the stimulation of Kupffer cells via complement mobilization is necessary but is not the only factor contributing to the early pathogenesis of hepatic injury following hindlimb I/R.

scholarly journals Hepatic Mrp4 induction following acetaminophen exposure is dependent on Kupffer cell function

2008 ◽  
Vol 295 (2) ◽  
pp. G294-G304 ◽  
Author(s):  
Sarah N. Campion ◽  
Rachel Johnson ◽  
Lauren M. Aleksunes ◽  
Michael J. Goedken ◽  
Nico van Rooijen ◽  
...  
Keyword(s):  
Kupffer Cell ◽  
Kupffer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Cell Depletion ◽  
Transporter Protein ◽  
Associated Proteins ◽  
Hepatic Transporters ◽  
Hepatic Transporter ◽  
Apap Hepatotoxicity

During acetaminophen (APAP) hepatotoxicity, increased expression of multidrug resistance-associated proteins 2, 3, and 4 (Mrp2-4) occurs. Mrp4 is the most significantly upregulated transporter in mouse liver following APAP treatment. Although the expression profiles of liver transporters following APAP hepatotoxicity are well characterized, the regulatory mechanisms contributing to these changes remain unknown. We hypothesized that Kupffer cell-derived mediators participate in the regulation of hepatic transporters during APAP toxicity. To investigate this, C57BL/6J mice were pretreated with clodronate liposomes (0.1 ml iv) to deplete Kupffer cells and then challenged with APAP (500 mg/kg ip). Liver injury was assessed by plasma alanine aminotransferase and hepatic transporter protein expression was determined by Western blot and immunohistochemistry. Depletion of Kupffer cells by liposomal clodronate increased susceptibility to APAP hepatotoxicity. Although increased expression of several efflux transporters was observed after APAP exposure, only Mrp4 was found to be differentially regulated following Kupffer cell depletion. At 48 and 72 h after APAP dosing, Mrp4 levels were increased by 10- and 33-fold, respectively, in mice receiving empty liposomes. Immunohistochemistry revealed Mrp4 staining confined to centrilobular hepatocytes. Remarkably, Kupffer cell depletion completely prevented Mrp4 induction by APAP. Elevated plasma levels of TNF-α and IL-1β were also prevented by Kupffer cell depletion. These findings show that Kupffer cells protect the liver from APAP toxicity and that Kupffer cell mediators released in response to APAP are likely responsible for the induction of Mrp4.

PROINFLAMMATORY KUPFFER CELL ALTERATIONS AFTER FEMUR FRACTURE TRAUMA AND SEPSIS IN RATS

Shock ◽  
2000 ◽  
Vol 14 (5) ◽  
pp. 555-560 ◽  
Author(s):  
Toan Huynh ◽  
John J. Lemasters ◽  
Lynette W. Bracey ◽  
Christopher C. Baker
Keyword(s):  
Kupffer Cell ◽  
Femur Fracture ◽  
Cell Alterations

scholarly journals Effects of Forskolin on Kupffer Cell Production of Interleukin-10 and Tumor Necrosis Factor Alpha Differ from Those of Endogenous Adenylyl Cyclase Activators: Possible Role for Adenylyl Cyclase 9

2005 ◽  
Vol 73 (11) ◽  
pp. 7290-7296 ◽  
Author(s):  
Maria K. Dahle ◽  
Anders E. Myhre ◽  
Ansgar O. Aasen ◽  
Jacob E. Wang
Keyword(s):  
Adenylyl Cyclase ◽  
Kupffer Cell ◽  
Kupffer Cells ◽  
Interleukin 10 ◽  
Prostaglandin E ◽  
Adenylyl Cyclases ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha

ABSTRACT Proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) that are released from Kupffer cells may trigger liver inflammation and damage. Hence, endogenous mechanisms for limiting TNF-α expression are crucial for avoiding the development of sepsis. Such mechanisms include the anti-inflammatory actions of interleukin-10 (IL-10) as well as signaling induced by the intracellular second messenger cyclic AMP (cAMP). Kupffer cells express several receptors that activate cAMP synthesis, including E-prostanoid receptors and β-adrenergic receptors. The expression and role of specific adenylyl cyclases in the inhibition of Kupffer cell activation have so far not been subject to study. Pretreatment of rat Kupffer cell cultures with cAMP analogues [8-(4-chlorophenyl)-thio-cAMP], adenylyl cyclase activator (forskolin), or ligands for G-coupled receptors (isoproterenol or prostaglandin E2) 30 min before the addition of lipopolysaccharide (LPS) (1 μg/ml) caused attenuated TNF-α levels in culture medium (forskolin/isoproterenol, P ≤ 0.05; prostaglandin E2, P ≤ 0.01). Forskolin also reduced IL-10 mRNA and protein (P ≤ 0.05), which was not observed with the other cAMP-inducing agents. Furthermore, we found that rat Kupffer cells express high levels of the forskolin-insensitive adenylyl cyclase 9 compared to whole liver and that this expression is down-regulated by LPS (P ≤ 0.05). We conclude that regulation of TNF-α and IL-10 in Kupffer cells depends on the mechanism by which cAMP is elevated. Forskolin and prostaglandin E2 differ in their effects, which suggests a possible role of forskolin-insensitive adenylyl cyclases like adenylyl cyclase 9.

Suppression of Kupffer cell function prevents cadmium induced hepatocellular necrosis in the male Sprague-Dawley rat

Toxicology ◽  
1997 ◽  
Vol 121 (2) ◽  
pp. 155-164 ◽  
Author(s):  
John-Michael Sauer ◽  
Michael P Waalkes ◽  
Stephen B Hooser ◽  
Robert K Kuester ◽  
Charlene A McQueen ◽  
...  
Keyword(s):  
Kupffer Cell ◽  
Cell Function ◽  
Sprague Dawley ◽  
Hepatocellular Necrosis ◽  
Sprague Dawley Rat

scholarly journals Epigenetic Regulation of Kupffer Cell Function in Health and Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Hunter Bennett ◽  
Ty D. Troutman ◽  
Mashito Sakai ◽  
Christopher K. Glass
Keyword(s):  
Transcription Factors ◽  
Kupffer Cell ◽  
Kupffer Cells ◽  
Cell Function ◽  
The Body ◽  
Alcoholic Fatty Liver ◽  
Liver Sinusoids ◽  
Health And Disease ◽  
And Function ◽  
Alcoholic Fatty Liver Disease

Kupffer cells, the resident macrophages of the liver, comprise the largest pool of tissue macrophages in the body. Within the liver sinusoids Kupffer cells perform functions common across many tissue macrophages including response to tissue damage and antigen presentation. They also engage in specialized activities including iron scavenging and the uptake of opsonized particles from the portal blood. Here, we review recent studies of the epigenetic pathways that establish Kupffer cell identity and function. We describe a model by which liver-environment specific signals induce lineage determining transcription factors necessary for differentiation of Kupffer cells from bone-marrow derived monocytes. We conclude by discussing how these lineage determining transcription factors (LDTFs) drive Kupffer cell behavior during both homeostasis and disease, with particular focus on the relevance of Kupffer cell LDTF pathways in the setting of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

scholarly journals Alteration of Kupffer Cell Function and Morphology by Low Melt Point Paraffin Wax in Female Fischer-344 but Not Sprague-Dawley Rats

1998 ◽  
Vol 46 (1) ◽  
pp. 176-184 ◽  
Author(s):  
N. C. Hoglen ◽  
S. P. Regan ◽  
J. L. Hensel ◽  
H. S. Younis ◽  
J-M. Sauer ◽  
...  
Keyword(s):  
Kupffer Cell ◽  
Cell Function ◽  
Paraffin Wax ◽  
Sprague Dawley ◽  
Fischer 344 ◽  
Sprague Dawley Rats
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