共查询到20条相似文献,搜索用时 31 毫秒
1.
John P. Scamman John K. Zawacki B. Jane McMurrich Bernard M. Babior 《Biochimica et Biophysica Acta (BBA)/General Subjects》1975,404(2):281-288
The acid glycosidase content of rat liver Kupffer cells was compared with that of hepatocytes and resident peritoneal macrophages. Homogenates of all these cells were able to hydrolyze the p-nitrophenyl glycosides of N-acetylglucosamine, N-acetylgalactosamine, glucose, galactose, fucose and mannose, but not xylose. Activity was greatest against the N-acetylglucosaminoside. With Kupffer cell homogenates, most of the glycosidases behaved as if they were lysosomal enzymes.When expressed as rates of hydrolysis per 106 cells, activities against a given substrate by homogenates from the three cell types generally agreed within a factor of 2–4. Significant differences between cell types were found, however, when ratios of glycosidase activities were compared. Furthermore, even though the quantity of glycosidase per cell was similar in Kupffer cells and hepatocytes, the glycosidase concentrations were much higher in the former cells, since Kupffer cells are much smaller than hepatocytes. 相似文献
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3.
FUMIO FUKAI YOSHITAKA SUZUKI YOSHINORI NISHIZAWA TAKASHI KATAYAMA 《Cell biology international》1996,20(6):423-428
We previously proposed that an enzymatic cooperation between Kupffer cells and hepatocytes may play an important role in cysteinyl leukotriene (LT) production in rat liver. Anin vitrotranscellular synthesis cysteinyl LTs by a Kupffer cell—hepatocyte coculture system was characterized here. Kupffer cells alone, with A23187 stimulation, did not generate cysteinyl LTs until supplemented either with isolated hepatocytes or with LTC4synthase and glutathione, indicating that Kupffer cells can synthesize LTA4but not convert it into LTC4. In contrast, hepatocytes converted the LTA4into cysteinyl LTs and further degraded the cysteinyl LTs. Cysteinyl LT production by the Kupffer cell—hapatocyte coculture system was optimized by addition of 1–3% serum albumin to the culture and by bringing the cell—cell distance closer to less than 3μ. Tumour necrosis factor also stimulated cysteinyl LT production by the coculture system. From these results, it is expected that the Kupffer cell—hepatocyte transcellular system for cysteinyl LT production actually functionsin vivo. 相似文献
4.
AimsHepatic fibrosis is reversible, associated with apoptosis of activated hepatic stellate cells (HSCs) as injury subsides, thus providing potential targets for therapy. Little is known, however, about the course of this condition. The objective of this study was to elucidate the mechanism by which Kupffer cells regulate HSC biology during regression of hepatic fibrosis and the effect of leflunomide on this process.Main methodsWe harvested Kupffer cells from rats during spontaneous recovery from liver fibrosis induced by carbon tetrachloride (CCl4) and prepared recovery Kupffer cell conditioned medium (KCCM). Culture-activated HSCs were pretreated in the absence or presence of A771726, the active metabolite of leflunomide, and then stimulated with recovery KCCM.Key findingsFollowing stimulation with recovery KCCM, HSCs showed a decrease in proliferation and an increase in apoptosis by a caspase-dependent mechanism. Furthermore, pretreatment with A771726 markedly enhanced these effects. Real-time quantitative PCR (Q-PCR) analysis showed increased expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Kupffer cells during the spontaneous recovery phase. The pro-apoptotic function of KCCM prepared from TRAIL siRNA-treated Kupffer cells was obviously decreased, suggesting that TRAIL played an important role in recovery from hepatic fibrosis. Moreover, A771726 enhanced recovery KCCM-induced apoptosis of HSCs by a mechanism involving the inhibition of nuclear factor-kappa B (NF-κB) activation.SignificanceOur results showed the role of TRAIL in the apoptosis of activated HSCs that is induced by Kupffer cells prepared from livers recovering from CCI4-induced fibrosis and provided insights into the resolution of fibrosis and the mechanisms by which leflunomide might act upon liver fibrosis. 相似文献
5.
Plasmodium yoelii sporozoites modulate cytokine profile and induce apoptosis in murine Kupffer cells
Plasmodium sporozoites traverse Kupffer cells on their way into the liver. Sporozoite contact does not elicit a respiratory burst in these hepatic macrophages and blocks the formation of reactive oxygen species in response to secondary stimuli via elevation of the intracellular cAMP concentration. Here we show that increasing the cAMP level with dibutyryl cyclic adenosine monophosphate (db-cAMP) or isobutylmethylxanthine (IBMX) also modulates cytokine secretion in murine Kupffer cells towards an overall anti-inflammatory profile. Stimulation of Plasmodium yoelii sporozoite-exposed Kupffer cells with lipopolysaccharide or IFN-γ reveals down-modulation of TNF-α, IL-6 and MCP-1, and up-regulation of IL-10. Prerequisite for this shift of the cytokine profile are parasite viability and contact with Kupffer cells, but not invasion. Whilst sporozoite-exposed Kupffer cells become TUNEL-positive and exhibit other signs of apoptotic death such as membrane blebbing, nuclear condensation and fragmentation, sporozoites remain intact and appear to transform to early exo-erythrocytic forms in Kupffer cell cultures. Together, the in vitro data indicate that Plasmodium possesses mechanisms to render Kupffer cells insensitive to pro-inflammatory stimuli and eventually eliminates these macrophages by forcing them into programmed cell death. 相似文献
6.
Yamamoto T Kaizu C Kawasaki T Hasegawa G Umezu H Ohashi R Sakurada J Jiang S Shultz L Naito M 《Cell and tissue research》2008,332(2):245-256
We previously reported that macrophage colony-stimulating factor (M-CSF, CSF-1) played important roles in the process of the
repopulation of Kupffer cells after their elimination by administration of liposome-entrapped dichloromethylene diphosphonate
(lipo-MDP). In this study, we examined the repopulation of Kupffer cells and splenic red pulp macrophages in osteopetrotic
(op/op) mice defective in the production of functional M-CSF and their littermate mice by using the lipo-MDP model. In untreated
op/op mice, numbers of F4/80-positive Kupffer cells in the liver and F4/80-positive splenic red pulp macrophages were reduced.
Repopulation of Kupffer cells and splenic macrophages was observed in littermate (op/+) mice liver by 14 days after depletion. However, in op/op mice, repopulation of Kupffer cells was not observed in Kupffer-cell-depleted op/op mice until 56 days after depletion, whereas splenic red pulp macrophages repopulated and recovered to the level of control
op/op mice by 10 days after depletion. Single injection of M-CSF was effective for the induction of the repopulation of Kupffer
cells, and daily administration of M-CSF induced remarkable repopulation and maturation of Kupffer cells and proliferation
of macrophage precursor cells in the liver of Kupffer-cell-depleted op/op mice. These results suggest that Kupffer cells are completely M-CSF-dependent tissue macrophages, whereas splenic red pulp
macrophages are composed of M-CSF-dependent macrophages and M-CSF-independent macrophages. This mouse model provides a useful
tool for the study of effects of growth factor on Kupffer cell differentiation in vivo.
This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture
of Japan, NIH grant CA20408, and a Tsukada Memorial Grant (2000). 相似文献
7.
The effect of kupffer cell stimulation or depression on the development of liver metastases in the rat 总被引:3,自引:0,他引:3
H. J. Pearson J. Anderson J. Chamberlain P. R. F. Bell 《Cancer immunology, immunotherapy : CII》1986,23(3):214-216
Summary Tumour cells from a squamous carcinoma (approximately 2.5×105) were injected intraportally into a syngeneic strain of rats to produce liver metastases 14 days later. Kupffer cells were stimulated by Corynebacterium parvum (7 mg or 1 mg i.v.) and zymosan (10 mg intraportally). Kupffer cell activity was depressed by the administration of silica, gadolinium chloride or human red cells. The animals in each group were sacrificed at 14 days, the livers removed and the number of visible surface metastases counted and compared. (Mann-Whitney U-test).Kupffer cell stimulation significantly reduced the number of surface liver metastases in all animals (P0.0048). In contrast depression of Kupfer cell activity significantly increased the number of metastases in all animals (P0.0045), suggesting that the activity of these cells has an important effect on the development of liver metastases. 相似文献
8.
Small unilamellar vesicles consisting of sphingomyelin, cholesterol and phosphatidylserine in a molar ratio of 4:5:1 containing [3H]inulin as a marker of the aqueous space or [Me-14C]choline-labeled sphingomyelin as a marker of the lipid phase were injected intravenously into rats. After separation of the non-parenchymal cells into a Kupffer cell fraction and an endothelial cell fraction by elutriation centrifugation analysis of the radioactivity contents demonstrated that Kupffer cells were actively involved in the uptake of the vesicles whereas endothelial cells did not contribute at all. Uptake by total parenchymal cells was also substantial but, on a per cell base, significantly lower than that by the Kupffer cells. By comparising the fate of the [3H]inulin label and the [14C]sphingomyelin label it was concluded that release of liposomal lipid degradation products especially occurred from Kupffer cells rather than from parenchymal cells. In both cell types, however, substantial proportions of the 14C-label accumulated in the phosphatidylcholine fraction, indicating intracellular degradation of sphingomyelin and subsequent phosphatidylcholine synthesis. Treatment of the animals with the lysosomotropic agent chloroquine prior to liposome injection effectively blocked the conversion of the choline-labeled sphingomyelin into phosphatidylcholine in both cell types. This observation indicates that uptake of the vesicles occurred by way of an endocytic mechanism. 相似文献
9.
Tumor necrosis factor-α (TNF-α) is released from blood-free perfused rat liver by the fungal metabolite ochratoxin A. Here
we have identified Kupffer cells as the sole source of OTA-mediated cytokine release. If single cell preparation of Kupffer
cells, hepatocytes, or sinusoidal endothelial cells were prepared from rat livers, only Kupffer cells released TNF-α upon
incubation with 2.5 μmol/l OTA. OTA failed to induce TNF-α release in the blood-free perfused isolated rat liver when Kupffer
cells were blockedin vitro by 15 μmol/l gadolinium chloride. When rats were pretreatedin vivo with the Kupffer cell depleting clodronate liposomes, OTA-mediated TNF-α release was abrogated in the isolated perfused liver
model. 相似文献
10.
Cornelia Schultze Frank Hildebrand Sandra Noack Christian Krettek Christian Zeckey 《Biomarkers》2016,21(7):645-652
Context: Early diagnosis of complications after severe trauma by specific biomarkers remains difficult.Objective: Identify potential new biomarkers for early diagnosis of post-traumatic complications.Material and methods: Mice underwent pressure-controlled hemorrhage or sham procedure. Four hours later, genome-wide expression of isolated Kupffer cells was compared with controls using Affymetrix-Genechip-Expression-Analysis and real-time-PCR.Results: Expression analysis and real-time-PCR revealed a significant increase of gene expression of Cxcl10, Il4ra, Csf2rb2, Lcn2, and Gbp5.Conclusion: Cxcl10, Il4ra, Csf2rb2, Lcn2, and Gbp5 might represent new biomarkers for early diagnosis of post-traumatic complications, if they are linked to the development of post-traumatic complications. 相似文献
11.
Summary The Kupffer cells in the liver of the teleost fish, Pimelodus maculatus, are attached by desmosomes to the endothelial cells lining the sinusoids. These provide a strong attachment allowing them to resist the passage of blood. Following perfusion with India ink, both endothelial and Kupffer cells ingest India ink particles by pinocytosis and micropinocytosis. It is suggested that both cell types may represent two different functional states of the same cell. 相似文献
12.
《Redox report : communications in free radical research》2013,18(5):243-250
AbstractLiver oxidative stress, Kupffer cell functioning, and cell injury were studied in control rats and in animals subjected to L-3,3′,5-tri-iodothyronine (T3) and/or acute iron overload. Thyroid calorigenesis with increased rates of hepatic O2 uptake was not altered by iron treatment, whereas iron enhanced serum and liver iron levels independently of T3. Liver thiobarbituric acid reactants formation increased by 5.8-, 5.7-, or 11.0-fold by T3, iron, or their combined treatment, respectively. Iron enhanced the content of protein carbonyls independently of T3 administration, whereas glutathione levels decreased in T3- and iron-treated rats (54%) and in T3Fe-treated animals (71%). Colloidal carbon infusion into perfused livers elicited a 109% and 68% increase in O2 uptake in T3 and iron-treated rats over controls. This parameter was decreased (78%) by the joint T3Fe administration and abolished by gadolinium chloride (GdCl3) pretreatment in all experimental groups. Hyperthyroidism and iron overload did not modify the sinusoidal efflux of lactate dehydrogenase, whereas T3Fe-treated rats exhibited a 35-fold increase over control values, with a 54% reduction by GdCl3 pretreatment. Histological studies showed a slight increase in the number or size of Kupffer cells in hyperthyroid rats or in iron overloaded animals, respectively. Kupffer cell hypertrophy and hyperplasia with presence of inflammatory cells and increased hepatic myeloperoxidase activity were found in T3Fe-treated rats. It is concluded that hyperthyroidism increases the susceptibility of the liver to the toxic effects of iron, which seems to be related to the development of a severe oxidative stress status in the tissue, thus contributing to the concomitant liver injury and impairment of Kupffer cell phagocytosis and particle-induced respiratory burst activity. 相似文献
13.
Hyperthyroidism enhances the prooxidant activity of the liver by elevating superoxide radical and/or hydrogen peroxide generation in microsomal, mitochondrial, and peroxisomal fractions, with an increased respiratory burst of Kupffer cells. In this study, the influence of daily doses of 0.1 mg 3,3′,5-triiodothyronine (T3)/kg for three consecutive days on liver nitric oxide (NO) synthase (NOS) was assessed, as a possible contributory mechanism to T3-induced liver prooxidant activity. Thyroid calorigenesis was paralleled by a progressive increment in the rate of NO generation, with significant increases after 2 (47%) and 3 days (70%) of T3treatment, and a net 45% (P< 0.05) enhancement in theNG-methyl-l-arginine-sensitive NO production, compared to control values. These enhancement effects were reversed to control levels after 3 days of hormone withdrawal, concomitantly with the normalization of hepatic respiration. Enhancement of liver NOS activity in hyperthyroid animals was diminished by 27% (P< 0.05) by the selectivein vivoinactivation of Kupffer cells by gadolinium chloride (GdCl3), without direct actions of GdCl3on the enzyme. These data demonstrate that hyperthyroidism leads to a significant and reversible enhancement in rat liver NOS activity, an effect that is exerted at hepatocyte and Kupffer cell levels, thus representing an additional source of prooxidants to those of reactive oxygen species. 相似文献
14.
Background
Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response.Aims
The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells.Methods
Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells.Results
High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis.Conclusion
High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD. 相似文献15.
16.
Kristin Andersland Guro F. Jølle Olav Sand Trude M. Haug 《The Journal of membrane biology》2010,235(2):121-129
Certain antimicrobial peptides from multicellular animals kill a variety of tumor cells at concentrations not affecting normal
eukaryotic cells. Recently, it was reported that also plantaricin A (PlnA), which is a peptide pheromone with strain-specific
antibacterial activity produced by Lactobacillus plantarum, permeabilizes cancerous rat pituitary cells (GH4 cells), whereas normal rat anterior pituitary cells are resistant to the peptide. To examine whether the preferential permeabilization
of cancerous cells is a general feature of PlnA, we studied its effect on primary cultures of cells from rat liver (hepatocytes,
endothelial, and Kupffer cells) and rat kidney cortex, as well as two epithelial cell lines of primate kidney origin (Vero
cells from green monkey and human Caki-2 cells). The Vero cell line is derived from normal cells, whereas the Caki-2 cell
line is derived from a cancerous tumor. The membrane effects were studied by patch clamp recordings and microfluorometric
(fura-2) monitoring of the cytosolic concentrations of Ca2+ ([Ca2+]i) and fluorophore. In all the tested cell types except Kupffer cells, exposure to 10–100 μM PlnA induced a nearly instant
permeabilization of the membrane, indicated by the following criteria: increased membrane conductance, membrane depolarization,
increased [Ca2+]i, and diffusional loss of fluorophore from the cytosol. At a concentration of 5 μM, PlnA had no effect on any of the cell
types. The Kupffer cells were permeabilized by 500 μM PlnA. We conclude that the permeabilizing effect of PlnA is not restricted
to cancerous cells. 相似文献
17.
Shusuke Hashimoto Yoshiyuki Seyama Teruo YOkokura Masahiko Mutai 《Cancer immunology, immunotherapy : CII》1985,20(2):117-121
Summary The ability of Kupffer cells, spleen macrophages, pulmonary macrophages, and peritoneal macrophages (PM) to produce cytotoxic factor (CTF) was investigated in vitro. The production of CTF by Kupffer cells elicited with Corynebacterium parvum (CP) or Lactobacillus casei YIT9018 (LC9018) was higher than that of spleen, pulmonary macrophages, or PM. In addition, oxygen radical (OR) production by Kupffer cells or PM was measured. The production of OR by Kupffer cells or PM was significantly augmented by i.v. or i.p. injection of LC9018 or CP. No significant correlation was observed between the increase in OR production by Kupffer cells or PM and CTF production by Kupffer cells or PM elicited with either organism. It was suggested that activated Kupffer cells may be one important source of CTF production in serum and that the CTF-producing macrophages may be different from the OR-producing macrophages. 相似文献
18.
G. Tapia P. Cornejo J. Ferreira V. Fernández 《Redox report : communications in free radical research》2013,18(4):213-218
SummaryThe influence of acetaminophen (APAP) treatment (400 mg/kg) on Kupffer cell function was studied in the isolated perfused liver by colloidal carbon infusion, concomitantly with parameters related to oxidative stress (thiobarbituric acid reactants (TBARS) formation and glutathione (GSH) content) and tissue injury (sinusoidal efflux of lactate dehydrogenase (LDH)). APAP led to increased rates of hepatic TBARS formation, GSH depletion, and higher sinusoidal LDH efflux compared to control values, without changes in the basal rate of O2 consumption. In addition, APAP significantly enhanced the rate of carbon uptake by perfused livers and the associated carbon-induced O2 consumption, with carbon-induced LDH effluxes being increased by 411% over control values or by 124% compared to basal LDH release in APAP-treated rats. APAP-induced changes in liver TBARS formation and GSH levels were attenuated by gadolinium chloride (GdCl3) pretreatment, whereas those in carbon uptake, carbon-induced respiration, and LDH efflux were abolished. GdCl3 pretreatment decreased liver O2 consumption irrespectively of APAP treatment, an effect that seems to be due to depression of mitochondrial respiration. It is concluded that APAP intoxication enhances Kupffer cell function as assessed in the intact liver, which may represent an important source of reactive O2 species and chemical mediators conditioning the increased oxidative stress status and the tissue injury which developed. 相似文献
19.
SHEILA CHIC J. SHIN JEROME P. VANDERBERG JOHN A. TERZAKIS 《The Journal of eukaryotic microbiology》1982,29(3):448-454
ABSTRACT. To identify the unknown liver cell type initially invaded by sporozoiles of mammalian malaria, young rats were inoculated intravenously with large numbers of Plasmodium berghei sporozoites obtained from infected Anopheles stephensi mosquitoes. Fine structural studies of liver specimens obtained from the rats within 2 min after inoculation demonstrated the presence of morphologically unaltered sporozoites in the cytoplasm of hepatocytes. Many sporozoites were also observed undergoing cytolysis within the lysophagosomes of Kupffer cells, as well as other phagocytic cells. These observations strongly suggest direct infection of the hepatocyte by the sporozoite. 相似文献
20.
Virginia Fernandez Luis A. Videla Gladys Tapia Yedy Israel 《Free radical research》2013,47(7):719-725
Thyroid hormone-induced calorigenesis contributes to liver oxidative stress and promotes an increased respiratory burst activity in Kupffer cells, which could conceivably increase the expression of redox-sensitive genes, including those coding for cytokines. Our aim was to test the hypothesis that l -3,3',5-triiodothyronine (T3)-induced liver oxidative stress would markedly increase the production of TNF- α by Kupffer cells and its release into the circulation. Sprague-Dawley rats received a single dose of 0.1 mg T3/kg or vehicle (controls) and determinations of liver O2 consumption, serum TNF-α, rectal temperature, and serum T3 levels, were carried out at different times after treatment. Hepatic content of total reduced glutathione (GSH) and biliary glutathione disulfide (GSSG) efflux were measured as indices of oxidative stress. In some studies, prior to T3 injection animals were administered either (i) the Kupffer cell inactivator gadolinium chloride (GdCl3), (ii) the antioxidants α-tocopherol and N-acetyl-L-cysteine (NAC), or (iii) an antisense oligonucleotide against TNF-α (ASO TJU-2755). T3 elicited an 80-fold increase in the serum levels of TNF-α at 22h after treatment, which coincided with the onset of thyroid calorigenesis. Pretreatment with GdCl3 , α-tocopherol, NAC, and ASO TJU-2755 virtually abolished this effect and markedly reduced T3-induced liver GSH depletion and the increases in biliary GSSG efflux. It is concluded that the hyperthyroid state in the rat increases the circulating levels of TNF-α by actions exerted at the Kupffer cell level and these are related to the oxidative stress status established in the liver by thyroid calorigenesis. 相似文献