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LBP/CD14系统及其与内毒素作用的关系 总被引:8,自引:0,他引:8
近年来,人们发现一组机体识别和调控内毒素(ET)作用的蛋白质分子:即LBP/CD14系统:包括血清脂多糖结合蛋白(LBP)、细胞表面膜结合CD14和可溶性CD14。LBP是ET的重要载体蛋白,mCD14是单核/巨噬细胞等CD14^+细胞表面的内毒素受体,sCD14则是调节内皮细胞等CD14细胞的重要介质。LBP/CD14系统能明显提高各种细胞对ET的敏感性,与脓毒症的发病机制有着密切的内在联系。 相似文献
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ZhenBin Mu Hua Wang Jing Zhang QingFang Li LiSheng Wang XiaoZhong Guo 《中国科学C辑(英文版)》2008,51(7):648-654
We conducted a study concerning the suppressive mechanism of KAI1/CD82 on hepatoma cell metastasis. Hepatocyte growth factor
(HGF) induces the migration of hepatoma cells through activation of cellular sphingosine kinase 1 (SphK1). Adenovirus-mediated
gene transfer of KAI1 (Ad-KAI1) downregulates the SphK1 expression and suppresses the HGF-induced migration of SMMC-7721 human
hepatocellcular carcinoma cells. Overexpression of KAI1/CD82 significantly elevates Sprouty2 at the protein level. Ablation
of Sprouty2 with RNA interference can block the KAI1/CD82-induced suppression of hepatoma cell migration and downregulation
of SphK1 expression. It is demonstrated that KAI1/CD82 suppresses HGF-induced migration of hepatoma cells via upregulation
of Sprouty2. 相似文献
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Effects of lead acetate on sensitivity to shock, intravascular carbon and endotoxin clearances, and hepatic endotoxin detoxification 总被引:3,自引:0,他引:3
J P Filkins B J Buchanan 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1973,142(2):471-475
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MU ZhenBin WANG Hua ZHANG Jing LI QingFang WANG LiSheng & GUO XiaoZhong 《中国科学:生命科学英文版》2008,51(7):648-654
We conducted a study concerning the suppressive mechanism of KAI1/CD82 on hepatoma cell metastasis.Hepatocyte growth factor(HGF)induces the migration of hepatoma cells through activation of cellular sphingosine kinase 1(SphK1).Adenovirus-mediated gene transfer of KAI1(Ad-KAI1)downregulates the SphK1 expression and suppresses the HGF-induced migration of SMMC-7721 human hepatocellcular carcinoma cells.Overexpression of KAI1/CD82 significantly elevates Sprouty2 at the protein level.Ablation of Sprouty2 with RNA interference can block the KAI1/CD82-induced suppression of hepatoma cell migration and downregulation of SphK1 expression.It is demonstrated that KAI1/CD82 suppresses HGF-induced migration of hepatoma cells via upregulation of Sprouty2. 相似文献
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Transfer of monomeric endotoxin from MD-2 to CD14: characterization and functional consequences 总被引:1,自引:0,他引:1
Teghanemt A Prohinar P Gioannini TL Weiss JP 《The Journal of biological chemistry》2007,282(50):36250-36256
Potent Toll-like receptor 4 (TLR4)-dependent cell activation by endotoxin depends on sequential transfer of monomers of endotoxin from an aggregated form to CD14 via the lipopolysaccharide-binding protein and then to MD-2. We now show that monomeric endotoxin can be transferred in reverse from MD-2 to CD14 but not to lipopolysaccharide-binding protein. Reverse transfer requires an approximately 1000-fold molar excess of CD14 to endotoxin-MD-2. Transfer of endotoxin from MD-2 to extracellular soluble CD14 reduces activation of cells expressing TLR4 without MD-2. However, transfer of endotoxin from MD-2 to membrane CD14 (mCD14) makes cells expressing MD-2.TLR4 sensitive to activation by the endotoxin-MD-2 complex. An endotoxin-mutant (F126A) MD-2 complex that does not activate cells expressing TLR4 alone potently activates cells expressing mCD14, MD-2, and TLR4 by transferring endotoxin to mCD14, which then transfers endotoxin to endogenous wild-type MD-2.TLR4. These findings describe a novel pathway of endotoxin transfer that provides an additional layer of regulation of cell activation by endotoxin. 相似文献
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Lipopolysaccharide (LPS, or endotoxin), is a major constituent of the outer membrane of Gram-negative bacteria. Bacteria express either smooth LPS, which is composed of O-antigen (O-Ag), complete core oligosaccharides, and the lipid A, or rough LPS which lack O-Ag but possess lipid A and progressively shorter core oligosaccharides. CD14 has been described as the receptor for complexes of LPS with LPS-binding protein (LBP). Using flow cytometry we have compared the binding of Salmonella minnesota rough LPS (ReLPS) and Escherichia coli smooth LPS labelled with fluorescein isothiocyanate (FITC-LPS) to Chinese hamster ovary (CHO) cells transfected with human CD14 gene (hCD14-CHO), to MonoMac 6 cells and to endothelial cells. Our results showed that both forms of LPS display the same binding characteristics, and that the binding of FITC-LPS to cells was both CD14- and LBP-dependent for LPS concentrations up to 100 ng.mL-1. At LPS concentrations higher than 100 ng.mL-1 we observed CD14/LBP-independent binding. CD14/LBP-dependent binding was dose dependent, saturable, and enhanced in the presence of human pooled serum (HPS), and the monoclonal anti-CD14 antibody (MY4) or unlabelled LPS could outcompete it. 相似文献
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Induction of TNF-alpha and MnSOD by endotoxin: role of membrane CD14 and Toll-like receptor-4 总被引:2,自引:0,他引:2
Tsan MF Clark RN Goyert SM White JE 《American journal of physiology. Cell physiology》2001,280(6):C1422-C1430
Endotoxin (LPS) is a potent inducer oftumor necrosis factor- (TNF-) and manganese superoxide dismutase(MnSOD). Recent evidence suggests that LPS induction of TNF- andMnSOD mRNAs is mediated through distinct intracellular signaltransduction pathways. Membrane CD14 (mCD14) and Toll-like receptor-4(TLR4) mediate LPS induction of TNF- in macrophages. In the current study, we evaluated the role of mCD14 and TLR4 in LPS induction ofMnSOD using peritoneal macrophages from CD14 knockout (CD14-KO) miceand mice with the Tlr4 gene point mutation (C3H/HeJ) ordeletion (C57BL/10ScCr). We studied mCD14-dependent (1 and 10 ng/ml)and mCD14-independent (1,000 ng/ml) concentrations of LPS. Compared with control (BALB/c) macrophages, LPS at 1 and 10 ng/ml failed toinduce TNF- or MnSOD mRNA in CD14-KO macrophages. However, LPS at1,000 ng/ml induced TNF- and MnSOD mRNAs equally in macrophages fromCD14-KO and control mice. LPS (1, 10, or 1,000 ng/ml) failed to induceTNF- or MnSOD mRNA and failed to activate nuclear factor-B inC3H/HeJ or C57BL/10ScCr macrophages. Measurements of TNF- and MnSODenzyme activity paralleled TNF- and MnSOD mRNA levels. These datademonstrate that, like TNF-, induction of MnSOD by LPS is mediatedby mCD14 and TLR4 in murine macrophages. 相似文献
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Lipopolysaccharide/endotoxin induces IL-18 via CD14 in human peripheral blood mononuclear cells in vitro 总被引:1,自引:0,他引:1
Manigold T Böcker U Traber P Dong-Si T Kurimoto M Hanck C Singer MV Rossol S 《Cytokine》2000,12(12):1788-1792
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Chmielinska JJ Tejero-Taldo MI Mak IT Weglicki WB 《Molecular and cellular biochemistry》2005,278(1-2):53-57
Substance P is elevated in plasma and in other tissues during Mg-deficiency, and was found localised to neuronal C-fibres
of cardiac and intestinal tissues, where it could promote neurogenic inflammation. Plasma prostaglandin E2 (PGE2), indicative of systemic inflammation, rose significantly (≥4 fold, p<0.01) after 1 week and remained elevated through week 2 and 3 in rat on the Mg-deficient (MgD) diet. Concomitantly, total
blood glutathione decreased by 50%. Immunohistochemical staining for endotoxin (lipopolysaccaride, LPS) receptor, CD14 was
prominent in macrophage-type cells in intestinal tissue; more importantly, cardiac tissue revealed both CD11b (monocyte/macrophage
surface protein) and CD14 positive cells after 3 weeks in rats on MgD diet. Western blot analysis indicated a significant
increase in the endotoxin receptor protein level in the 3 week MgD hearts. Since CD14 is known to be up-regulated in cells
exposed to LPS, these observations suggest that prolonged Mg-deficiency results in increased intestinal permeability to bacterial
products that induce the endotoxin receptor in cells localized to myocardial and intestinal tissues. These CD14 positive cells
may amplify the cardiomyopathic inflammatory process by stimulating TNF-α and other pro-inflammatory cytokines. (Mol Cell
Biochem 278: 53–57, 2005) 相似文献
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Albright S Chen B Holbrook K Jain NU 《Biochemical and biophysical research communications》2008,368(2):231-237
CD14 functions as a key pattern recognition receptor for a diverse array of Gram-negative and Gram-positive cell-wall components in the host innate immune response by binding to pathogen-associated molecular patterns (PAMPs) at partially overlapping binding site(s). To determine the potential contribution of CD14 residues in this pattern recognition, we have examined using solution NMR spectroscopy, the binding of three different endotoxin ligands, lipopolysaccharide, lipoteichoic acid, and a PGN-derived compound, muramyl dipeptide to a 15N isotopically labeled 152-residue N-terminal fragment of sCD14 expressed in Pichia pastoris. Mapping of NMR spectral changes upon addition of ligands revealed that the pattern of residues affected by binding of each ligand is partially similar and partially different. This first direct structural observation of the ability of specific residue combinations of CD14 to differentially affect endotoxin binding may help explain the broad specificity of CD14 in ligand recognition and provide a structural basis for pattern recognition. Another interesting finding from the observed spectral changes is that the mode of binding may be dynamically modulated and could provide a mechanism for binding endotoxins with structural diversity through a common binding site. 相似文献
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Impaired endotoxin detoxification as a factor in enhanced endotoxin sensitivity of malaria infected mice 总被引:14,自引:0,他引:14
L D Loose R Trejo N R Di Luzio 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1971,137(3):794-797
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Panaro MA Cianciulli A Gagliardi N Mitolo CI Acquafredda A Cavallo P Mitolo V 《FEMS immunology and medical microbiology》2008,53(1):35-45
CD14 is a surface differentiation antigen that functions as a receptor for bacterial lipopolysaccharide. The cellular signaling events that lead to lipopolysaccharide-induced production of inflammatory mediators are the primary cause of myocardial dysfunction observed in sepsis. Here, we evaluated the role of CD14 in chick embryo cardiomyocytes stimulated with lipopolysaccharide. CD14 expression was detected by confocal laser microscopy observation and by immunoblotting analysis. Moreover, we provided evidence for CD14-dependent functional responses of lipopolysaccharide-stimulated cardiomyocytes in terms of tumor necrosis factor (TNF)-alpha and nitric oxide (NO) production. Attenuated TNF-alpha and NO secretion, following anti-CD14 treatment of cardiomyocytes, suggested a role for this receptor in lipopolysaccharide-mediated cell responses. We also evidenced that labeled lipopolysaccharide was internalized and localized next to the Golgi complex, at the level of lysosomes, and in the perinuclear zone. The intracytoplasmatic transport seems to depend on the contractile apparatus, because cell pretreatment with cytochalasin D prevented lipopolysaccharide internalization and reduced both TNF-alpha and NO release. Lipopolysaccharide internalization was dependent on CD14 receptor, since anti-CD14 pre-treatment prevented endotoxin uptake by cardiomyocytes. Results demonstrated: (1) CD14 is expressed on the surface membrane of cardiomyocytes; (2) CD14 is involved in cytoskeletal dependent lipopolysaccharide internalization at specific cytoplasmatic locations; (3) CD14 plays a role in lipopolysaccharide-mediated responses by cardiomyocytes after lipopolysaccharide internalization. 相似文献
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Effects of endotoxin on myocardial hemodynamics, performance, and metabolism during beta adrenergic blockade 总被引:1,自引:0,他引:1
L B Hinshaw L J Greenfeild L T Archer C A Guenter 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1971,137(4):1217-1224
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Richard A. Winchurch William Birmingham Charles Hilberg Andrew Munster 《Cellular immunology》1982,67(2):384-389
In vivo administration of bacterial lipopolysaccharides (LPS) to young adult mice causes a dose-dependent depression of antibody formation. In contrast, LPS produced no effects on the responses of older mice and these animals appeared to be refractory to the depressive effects observed in the young adults. When young adults were pretreated with endotoxin their baseline control responses were also severely depressed and the LPS response profile resembled that of the normal 9-month-old animals. These results suggest that endotoxin effects may contribute to the genesis of immune abnormalities in the aged. 相似文献
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Effects of taxol on isolated rat hepatocyte metabolism 总被引:1,自引:0,他引:1
Manzano A.; Roig T.; Bermudez J.; Bartrons R. 《American journal of physiology. Cell physiology》1996,271(6):C1957
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Cholestasis inhibits expression of early response genes in rat hepatocytes stimulated to proliferation and restricts the process related to reparative regeneration. The occlusion of general bile duct induces bile acid accumulation, which suppresses 11-beta-hydroxysteroid-dehydrogenase activity. Hence, the concentration of corticosterone is increased, which suppresses the expression of early response genes in rat hepatocytes. The restoration of liver mass occurs due to proliferation of reserved cells. An unusual mitotic peak of these cells is registered 34 h after the operation. 相似文献