Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 52 kD myeloid membrane glycoprotein CD14 represents the receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP); it is involved in LPS induced tumor necrosis factor-alpha production. Expression of CD14 increases in monocytes differentiating into macrophages, and it is reduced by rIFNg in monocytes in vitro. In the present study CD14 membrane antigen expression was investigated in cultures of human mononuclear leucocytes (PBL), in elutriated, purified monocytes, and in blood monocyte derived Teflon cultured macrophages. Cells were incubated for 15 or 45 h with rIL-1, rIL-2, rIL-3, rIL-5, rIL-6, rTNFa, rGM-CSF, rM-CSF, rTGFb1, rIFNa, lipopolysaccharide (LPS), and, as a control, rIFNg. The monoclonal antibodies Leu-M3 and MEM 18 were used for labelling of CD14 antigen by indirect immunofluorescence and FACS analysis of scatter gated monocytes or macrophages. IFNg concentrations were determined in PBL culture supernatants by ELISA. rIFNa and rIL-2 reduced CD14 in 15 and 45 h PBL cultures, an effect mediated by endogenous IFNg, since it was abolished by simultaneous addition of an anti-IFNg antibody. rIFNa and rIL-2 were ineffective in purified monocytes or macrophages. rIL-4 strongly reduced CD14 in PBL and purified monocytes after 45 h, whereas in macrophages the decrease was weak, although measurable after 15 h. The other cytokines investigated did not change CD14 antigen expression. Cycloheximide alone reduced CD14, but when added in combination with rIFNg the effect on CD14 downregulation was more pronounced. The effect of rIFNg on CD14 in PBL cultures was dose-dependently inhibited by rIL-4 and this inhibition is probably due to an IL-4 mediated blockade of IFNg secretion. LPS at a low dose increased CD14, at a high dose it produced a variable decrease of CD14 in PBL, which was probably due to LPS induced IFNg secretion. LPS strongly enhanced CD14 in 45 h cultures of purified monocytes. The results, showing that CD14 antigen expression is upregulated by LPS and downregulated by rIFNg and rIL-4, suggest that the LPS-LBP receptor is involved in the feedback response of IFNg and IL-4 to LPS stimulation.
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PMID:Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages. 172 47

The macrophage scavenger receptor, a 220-kDa trimeric membrane glycoprotein, mediates the internalization of modified forms of low density lipoprotein (LDL) such as acetyl-LDL and oxidized-LDL and thus is likely to play a key role in atheroma macrophage foam cell formation. In addition, recent evidence suggests that the scavenger receptor may be an important macrophage binding site for lipopolysaccharide involved in lipopolysaccharide scavenging by macrophages. However, little is known about the regulation of this important receptor. We now report that the induction of scavenger receptor activity (as measured by acetyl-LDL stimulation of intracellular cholesterol esterification) seen in phorbol ester-differentiated THP-1 human macrophages was completely suppressed to the level seen in undifferentiated THP-1 monocytes by picomolar concentrations of transforming growth factor-beta 1 (TGF-beta 1). 125I-Acetyl-LDL degradation was inhibited in a dose-dependent manner by TGF-beta 1, with maximal inhibition (approximately 70%) occurring at 24 pM TGF-beta 1. Scatchard analysis revealed that TGF-beta 1 treatment resulted in a approximately 2-fold decrease in receptor number, and Northern blot analysis of RNA isolated from differentiated THP-1 macrophages demonstrated approximately 2-fold less scavenger receptor mRNA in TGF-beta 1-treated cells compared with that in macrophages not treated with TGF-beta 1. Since TGF-beta 1 is thought to be present in both atherosclerotic and inflammatory lesions, the above findings may have physiological relevance regarding the regulation of atheroma foam cell formation and/or the regulation of lipopolysaccharide clearance by macrophages.
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PMID:Transforming growth factor-beta 1 inhibits scavenger receptor activity in THP-1 human macrophages. 174 79

Tissue factor (TF) is an integral membrane glycoprotein which, as the receptor and essential cofactor for coagulation factors VII and VIIa (FVII and FVIIa, respectively), is the primary cellular activator of the coagulation protease cascade. Previous studies on the procoagulant activity of a variety of cell types (either lysed or in the intact state) have variously been interpreted as showing that TF is either stored intracellularly or is present in a cryptic form in the surface membrane. Using mAbs to TF, we have directly investigated the subcellular localization and functional activity of TF in lipopolysaccharide-stimulated blood monocytes and J82 bladder carcinoma cells. Blocking of surface TF of viable cells with inhibitory anti-TF mAbs abolished greater than 90% of TF activity of the intact cells as well as of lysed cells. Furthermore, quantitative analysis of the binding of FVII and anti-TF mAb to J82 cells demonstrated that all surface-expressed TF molecules were capable of binding the ligand, FVII. By immunoelectron microscopy, TF was present only in the surface membrane of monocytes and J82 cells, although the latter also contained apparently inactive TF antigen in multivesicular bodies. On the intact cell surface the catalytic activity of the TF-FVIIa complex was investigated and found to be markedly less relative to cell lysates. Membrane alterations that affect the cofactor activity of TF may be a means of regulating the extent of initiation of the coagulation protease cascade in various cellular settings.
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PMID:Functional tissue factor is entirely cell surface expressed on lipopolysaccharide-stimulated human blood monocytes and a constitutively tissue factor-producing neoplastic cell line. 266 80

Monoclonal antibodies were used as cytochemical markers to study surface interactions between endosymbiotic Rhizobium bacteroids from pea root nodules and the encircling peribacteroid membranes, which are of plant origin. Monoclonal antibodies that react with Rhizobium lipopolysaccharide (LPS) or with a plant membrane glycoprotein were used as markers for material from the bacteroid outer membrane or the peribacteroid membrane, respectively. Membrane-enclosed bacteroids were isolated from nodule homogenates by sucrose gradient centrifugation, and the encircling peribacteroid membrane was released by mild osmotic shock treatment. Using an immunochemical technique (sandwich ELISA), it was shown that 1-5% of the LPS antigen released into the peribacteroid fraction by mild osmotic shock treatment was physically associated with peribacteroid membrane through a detergent-sensitive linkage. This association could be visualized when freshly prepared peribacteroid material was immobilized on gold grids and examined by electron microscopy after dual antibody immunogold treatment and subsequent negative staining. The distribution of LPS antigen within infected nodule cells was also investigated by immunogold staining for thin sections of nodule tissue fixed in glutaraldehyde, and a close association between LPS antigen and peribacteroid membrane was often seen.
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PMID:Physical association between the peribacteroid membrane and lipopolysaccharide from the bacteroid outer membrane in Rhizobium-infected pea root nodule cells. 379 95

CD14, a glycolipid-anchored membrane glycoprotein, acts as a high affinity lipopolysaccharide receptor on leukocytes. We previously reported that the Mono-Mac-6 cell line releases two different soluble forms of CD14 (sCD14) (Labeta et al., Eur. J. Immunol. 1993. 23: 2144). Here we show that the two sCD14, which we now refer to as sCD14 alpha (low M(r)) and sCD14 beta (high M(r)), are also synthesized and released by normal human monocytes and present in normal plasma. Their mechanism of release was examined by using the Mono-Mac-6 cell line, chinese hamster ovary cell (CHO)/CD14+ transfectants and plasma from paroxysmal nocturnal hemoglobinuria (PNH) patients. It was found that: (1) sCD14 beta is released faster than sCD14 alpha and that the release of the latter is a lengthy process. (2) Monensin blocked the biosynthesis of membrane-bound CD14 (mCD14) and sCD14, additionally, a 50-kDa CD14 polypeptide accumulated in the cell lysate, suggesting that the different forms of CD14 may have a common precursor. (3) Monensin also blocked the release of sCD14 alpha from surface-labeled cells, suggesting that conversion of mCD14 to sCD14 alpha involves a mechanism of endocytosis followed by exocytosis. Interestingly, (4) sCD14 alpha and sCD14 beta were detected in PNH plasma, indicating that sCD14 alpha may also derive from an endogenous pathway. (5) Phospholipase C-released CD14 was identical in size to mCD14, thus differed from sCD14 beta by approximately 2000, indicating that release of sCD14 beta involves further processing. (6) CHO cells transfected with a CD14 cDNA coding for an eight C-terminal amino acids shorter product released an sCD14 beta-like form; thus absence of the eight C-terminal amino acids prevented mCD14 expression but not the secretion of sCD14 beta. The characterization of sCD14 alpha and sCD14 beta reported here may be useful for better understanding of variations in sCD14 levels in pathological conditions and the contribution of each sCD14 in sepsis and other, as yet unknown functions.
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PMID:The two soluble forms of the lipopolysaccharide receptor, CD14: characterization and release by normal human monocytes. 752 57

Vascular cell adhesion molecule-1 (VCAM-1) is an endothelial cell membrane glycoprotein that has been implicated in leukocyte/endothelial cell interactions in inflammation. In this study, we report the expression of VCAM-1 in primary cultures of human brain microvessel endothelial cells (HBMEC) under standard conditions and following bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or interferon-gamma (IFN-gamma) treatment. Surface expression was detected and quantitated by light and immunogold electron microscopy and ELISA. Unstimulated cerebral endothelial cells (EC) constitutively expressed low levels of VCAM-1. LPS, TNF-alpha, or IL-1 beta increased the overall intensity of surface staining and the percentage of cells expressing VCAM-1 in a time- and concentration-dependent manner. LPS had the most potent effect, followed by TNF-alpha and then IL-1 beta. IFN-gamma did not upregulate VCAM-1. The level of VCAM-1 expression increased by 12-24 hr and returned to unstimulated levels by 48 hr. Immunoelectron microscopy demonstrated that VCAM-1 was preferentially localized on the apical as compared to the basal surface in both unstimulated and cytokine-treated cells. In addition, the intensity of immunostaining was significantly greater in stimulated versus unstimulated EC. The polarization and significant upregulation of VCAM-1 after cytokine treatment suggest a possible role of this adhesion molecule in inflammatory and autoimmune processes within the central nervous system.
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PMID:Expression of vascular cell adhesion molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary culture. 754 72

The membrane inhibitor of reactive lysis (MIRL) is an 18-Kd glycosyl phosphatidylinositol anchored membrane glycoprotein that inhibits the cytolytic activity of complement. MIRL is expressed by all hematopoietic elements and by a wide variety of nonhematopoietic tissues. A deficiency of MIRL is primarily responsible for the greater sensitivity of the erythrocytes of paroxysmal nocturnal hemoglobinuria to complement mediated lysis. Because of its critical role in protecting host cells from injury by complement, we hypothesized that mechanisms exist that allow MIRL expression to be regulated. To investigate this hypothesis, both MIRL RNA and MIRL protein expression were analyzed following exposure of K562 erythroleukemia cells to a variety of potential stimulants. Incubation with dexamethasone, calcium ionophore, lipopolysaccharide, interleukin 1, tumor necrosis factor, hemin, and cyclic AMP had no effect on MIRL expression. However, incubation with phorbol 12-myristate 13 acetate (PMA), induced a marked increase in MIRL RNA as determined by Northern blot analysis. This enhanced expression of MIRL RNA was associated with an increase in MIRL protein expression as determined by immunoprecipitation of metabolically labeled proteins, Western blot analysis, and immunobinding assay. Enhanced MIRL RNA expression was first detected after 8 hours and increased through 24 hours of observation. Inhibitors of either protein synthesis or transcription abrogated the PMA-induced enhancement of MIRL RNA expression. Together, these results are consistent with a model in which PMA induces synthesis of a trans acting protein that enhances transcription of the MIRL gene.
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PMID:Enhanced expression of the complement regulatory protein, membrane inhibitor of reactive lysis (CD59), is regulated at the level of transcription. 768 99

Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for blood coagulation factor VIIa. The induction of TF on the surface of endothelial cells is initiated by various kinds of stimuli including lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha). The mechanisms leading to induction of TF are largely unknown and the present study explores the influence of calcium influx on TF induction in LPS-stimulated human umbilical vein endothelial cells. TF cofactor activity was measured on cell surfaces and in lysates by a two-stage chromogenic assay after the cells were incubated under a variety of conditions. TF activity of cell surfaces increased 3.3-fold above control values after LPS stimulation (100 ng/ml, 4 h). Addition of 20 microM A23187, a calcium ionophore, to the LPS-stimulated cells just before the TF assay, resulted in an additional 8.8-fold enhancement. TF activity of lysed cells increased 10.5-fold above control values after LPS stimulation (100 ng/ml). Incubation with lower concentrations of A23187 and 100 ng/ml-1 micrograms/ml LPS for 4 h resulted in activity twice that of LPS stimulation alone. The TF mRNA signal of LPS plus 1 microM A23187-treated cells was also increased in addition to LPS treated cells.
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PMID:The effect of calcium ionophore A23187 on tissue factor activity and mRNA in endothelial cells. 802 20

Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for the blood coagulation factor VIIa. The induction of TF synthesis and activity on the surface of endothelial cell membrane is initiated by lipopolysaccharide (LPS), phorbol 12-myristate 13-O-acetate (PMA), and inflammatory factors such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha). Treatment of cells with 1 micrograms/ml LPS induced an 8.7-fold increase in total TF activity compared with nontreated cells. Co-incubation with 1 micrograms/ml LPS and 30 microM W7, a potent calmodulin inhibitor, resulted an additional 2.0 fold increase in total TF activity. A similar tendency was observed after treatment with either TNF alpha plus W7, or IL-1 beta plus W7. The effect of W7 appeared to be synergistic since incubation with 30 microM W7 alone increased TF activity levels to only 1.5-fold that of control cells. Northern blot analysis showed that W7 and LPS-treated endothelial cells expressed about three times higher levels of TF mRNA compared to LPS-treated cells. Treatment with W7 and LPS resulted in a slow but large calcium influx into endothelial cells. This result suggest that the contribution of W7 may be dependent mainly on calcium influx by unknown mechanisms rather than direct inhibition of calmodulin, because calcium ionophore treatment also showed a synergistic effect on TF mRNA and activity expression.
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PMID:Up-regulation of tissue factor mRNA in human umbilical vein endothelial cells by calmodulin inhibitor W7. 819 11

Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for blood coagulation factor VIIa. The induction of TF on the surface of endothelial cells is initiated by various stimuli including lipopolysaccharide, interleukin-1 beta, and tumor necrosis factor alpha. We have demonstrated that recombinant human C5a induces TF activity in a dose-dependent fashion in human umbilical vein endothelial cells (HUVEC). Peak activity (4.9-fold increase) was obtained 3-6 h after treatment with 10 microM C5a. TF mRNA as assessed by RT-PCR method was also significantly increased (3.75-fold) after 3 h incubation with C5a, suggesting that C5a induces TF activity on HUVEC, at least in part, by enhancing the level of TF mRNA. The increase in TF activity by C5a was inhibited by methylprednisolone. The induction of TF on endothelial cells by C5a may represent one of many potential interrelationships between the inflammatory and coagulation schemes.
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PMID:C5a induces tissue factor activity on endothelial cells. 915 2


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