UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increased adherence of leukocytes to the vascular endothelium appears to be a crucial event in the development of atherosclerosis. The role of endothelial cell adhesion molecules is gaining increasingly interest in this context. Several studies show an influence of lipoproteins, especially low-density-lipoproteins on adhesion molecule stimulation. The aim of our study was to analyze the atherogenic potential of postprandially elevated serum triglyceride levels by investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated 4 h after a standard oral lipid load)) on the expression of E-selectin (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell adhesion molecule-1). In addition we used chylomicrons that had been incubated with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin lipopolysaccharide (LPS) served as positive control for adhesion molecule stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E-Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/- 324). In summary, chylomicrons induced an enhancement of the expression of both adhesion molecules, which closely resembled or even exceeded the endotoxin-induced stimulation. Interestingly, this effect was diminished or even reversed after incubation with LPL.
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PMID:Chylomicrons induce E-selectin and VCAM-1 expression in endothelial cells. 928 41

The contribution of E- and P-selectin in the rat to the migration of polymorphonuclear leucocytes (PMNL) and monocytes to acute dermal inflammation induced by a chemoattractant (C5ades Arg) or endothelial cell activating agents [lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), alpha-thrombin and interferon-gamma] administered intradermally was investigated. Migration was quantitated using radiolabelled blood PMNL and monocytes and new, function-blocking monoclonal antibodies (mAbs) to rat E- and P-selectin were employed. Monocyte migration to inflamed skin was partially inhibited (40-75%) by P-selectin mAb with all stimuli tested, but not by anti-E-selectin. PMNL migration in response to all stimuli was also inhibited (50-75%) by blocking P-selectin, but in contrast to monocytes, PMNL accumulation was partially inhibited by mAb to E-selectin in alpha-thrombin and TNF-alpha lesions. When P-selectin was blocked by mAb, mAb to E-selectin significantly inhibited further (by 70-90%) both PMNL and monocyte accumulation in all lesions, indicating that both P- and E-selectin contribute to the migration of these leucocytes. Blocking L-selectin in addition to P- and E-selectin, had no effect on the remaining migration. Thus, optimal PMNL and monocyte migration to chemotactic factor- and cytokine-induced skin inflammation is P-selectin dependent. E-selectin becomes important, in most conditions used here, when P-selectin mediated recruitment is not operative. A selectin independent pathway likely mediates up to 20% of PMNL and monocyte migration to acute inflammation, at least in skin.
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PMID:Role of E- and P-selectin in migration of monocytes and polymorphonuclear leucocytes to cytokine and chemoattractant-induced cutaneous inflammation in the rat. 941 39

Listeria monocytogenes infection of endothelial cells upregulates surface expression of adhesion molecules and stimulates neutrophil adhesion to infected cell monolayers. The experiments presented here tested the roles of specific bacterial virulence factors as triggers for this inflammatory phenotype and function. Human umbilical vein endothelial cell (HUVEC) monolayers were infected with wild-type L. monocytogenes or L. monocytogenes mutants; then surface expression of E-selectin and neutrophil adhesion were measured. The results showed that delta hly and prfA mutants were the most crippled, requiring 100-fold more mutant bacteria than wild-type bacteria for analogous stimulation. By comparison, L. monocytogenes mutants with deletions of actA, inlA, inlB, inlAB, plcA, and plcB resembled their parent strains, and a delta plcA delta plcB mutant displayed decreased intracellular growth rate but only a minor decrease in stimulation of E-selectin or neutrophil adhesion. Other experiments showed that cytochalasin D-treated HUVEC monolayers bound bacteria, but internalization and increased surface E-selectin and intercellular adhesion molecule-1 expression were profoundly inhibited. However, cytochalasin D had no effect on the HUVEC response to stimulation with lipopolysaccharide or tumor necrosis factor alpha. These data suggest that listeriolysin O production by infecting L. monocytogenes contributes to increased expression of surface E-selectin and intercellular adhesion molecule-1, but neither it nor intracellular replication are directly responsible for this event. Nonetheless it is possible that listeriolysin O potentiates the effect(s) of an other molecule(s) that directly triggers this response. Additionally, cellular invasion by L. monocytogenes appears to be critical for initiating the HUVEC response, potentially by providing a signal which results in upregulation of the necessary bacterial genes.
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PMID:Listeria monocytogenes virulence factors that stimulate endothelial cells. 942 63

We analyzed the influence of heavy-metal ions on human umbilical vein endothelial cells (HUVEC) in comparison to proinflammatory cytokines (TNF-alpha, IL-1beta) and lipopolysaccharide (LPS). Adhesion molecule and cytokine expressions are upregulated by heavy-metal exposure. Expression of E-selectin on the cell surface was strongly induced by 1-mM concentrations of NiCl2 and CoCl2, whereas ZnCl2 and CrCl3 had no influence. Furthermore, it is shown that NiCl2 induces mRNA expression of E-selectin, intercellular adhesion molecule-1, IL-6 and IL-8 in a 1-mM concentration. The transcription factor NF-kappaB is known to be involved in the regulation of adhesion molecule expression in endothelial cells after activation by proinflammatory cytokines. We demonstrated that treatment of HUVEC with Ni2+ and Co2+ ions induces the translocation of NF-kappaB p65 and also p50 into the nucleus. NF-kappaB binding activity is enhanced under the influence of heavy metals as determined by mobility shift analysis. P65 and p50 are components of the NF-kappaB complexes as confirmed by supershift analysis. We could show that activation at the protein level is accompanied by induction of NF-kappaB p65 mRNA expression. HUVEC also express the NF-kappaB inhibitor I kappaB-alpha (MAD-3). In the early phase of activation by Ni2+ and Co2+ ions, disappearance of I kappaB-alpha in the cytoplasm accompanied p65 translocation, followed by its gradual reappearence. Because I kappaB mRNA could be upregulated by NiCl2 as well as by a mixture of cytokines, we suggest that the replenishment of the inhibitor in the cytoplasm is caused by de novo I kappaB gene expression. In addition to the enhanced DNA-binding activity of NF-kappaB, another transcription factor, AP-1, was also augmented in HUVEC stimulated by NiCl2, CoCl2 or by proinflammatory mediators and the phorbol ester PMA. Fos protein is shown to be a component of the activated AP-1 complex, as determined by supershift analysis, suggesting that it consists of Jun/Fos heterodimers.
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PMID:Heavy metal ion induction of adhesion molecules and cytokines in human endothelial cells: the role of NF-kappaB, I kappaB-alpha and AP-1. 945 94

P-selectin, an adhesion receptor for leukocytes, is constitutively expressed in megakaryocytes and endothelial cells. Tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) increases synthesis of P-selectin in murine but not in human endothelial cells. To identify potential species-specific and conserved mechanisms for regulation of expression of P-selectin, we cloned the 5'-flanking region of the murine P-selectin gene and compared its features with those previously reported for the human gene. The murine and human genes shared conserved Stat-like, Hox, Ets, GATA, and GT-IIC elements. In the murine gene, a conserved GATA element bound to GATA-2 and functioned as a positive regulatory element, whereas a conserved Ets element bound to GA-binding protein and functioned as a negative regulatory element. Significantly, the murine P-selectin gene had several features not found in the human gene. These included an insertion from -987 to -649 that contained tandem GATA and tandem AP1-like sequences, which resembled enhancers in beta-globin locus control regions. Both tandem elements bound specifically to nuclear proteins. The murine gene lacked the unique kappaB site specific for p50 or p52 homodimers found in the human gene. Instead, it contained two tandem kappaB elements and a variant activating transcription factor/cAMP response element site, which closely resembled sites in the E-selectin gene that are required for TNF-alpha- or LPS-inducible expression. TNF-alpha or LPS augmented expression of a reporter gene driven by the murine, but not the human, P-selectin promoter in transfected endothelial cells. Deletional analysis of the murine 5'-flanking region revealed several sequences that were required for either constitutive or inducible expression. These data suggest that both species-specific and conserved mechanisms regulate transcription of the human and murine P-selectin genes.
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PMID:Comparison of promoters for the murine and human P-selectin genes suggests species-specific and conserved mechanisms for transcriptional regulation in endothelial cells. 954 53

Recent studies suggest that increased vascular cell adhesion molecule-1 (VCAM-1) expression on vascular endothelium in bronchial mucosa biopsies correlates with interleukin-4 (IL-4) levels in bronchiolar lavage fluid of allergic asthmatics. The severity of asthma in patients allergic to house dust mite has also been shown to correlate with lipopolysaccharide (LPS), rather than allergen, concentration in dust. We hypothesized that to induce effective VCAM-1 expression in human lung microvascular endothelial cells (HLMVEC), IL-4 may require the presence of a co-stimulus such as LPS. To test this hypothesis we measured, by enzyme-linked immunosorbent assay, induction of cell adhesion molecule expression on, and human eosinophil adhesion to, cultured HLMVEC monolayers pretreated with IL-4 alone or combined with LPS. IL-4 synergized with LPS to induce VCAM-1 expression at 24, 48, or 72 h, whereas IL-4 alone induced expression at 72 h only. IL-4 did not induce expression of intercellular adhesion molecule-1 or E-selectin or alter LPS-induced expression of either. Pre-exposure of HLMVEC to LPS or IL-4 (1 h), followed by IL-4 or LPS, respectively (23 h), also induced VCAM-1 expression. Eosinophil adhesion to HLMVEC monolayers treated with IL-4 and LPS together, but not alone, significantly (P < 0.001) increased from 9.6 +/- 1.5% (control) to 26.9 +/- 3.3% and was inhibited by a monoclonal antibody against the VCAM-1 ligand, very late antigen-4. Analysis of VCAM-1 mRNA revealed synergism between IL-4 and LPS which may, in part, contribute to enhanced VCAM-1 expression. These results suggest that the presence of a co-stimulus such as LPS may be necessary for IL-4 to effectively induce VCAM-1 expression in lung microvasculature.
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PMID:Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion molecule-1 expression in human lung microvascular endothelial cells. 956 32

We studied the capacity of isolated Bacteriodes fragilis outer membrane, B. fragilis NCTC9343 lipopolysaccharide (LPS; endotoxin), and B. fragilis NCTC9343 capsular polysaccharides to activate human umbilical vein endothelial cell (HUVEC) monolayers. To assess HUVEC activation, E-selectin expression was measured by enzyme-linked immunosorbent assay (ELISA), Northern blot analysis for E-selectin-specific mRNA, and electrophoretic gel mobility shift assay (EMSA) for NF-kappa B, a transcription factor necessary for E-selectin gene activation. Exposure of HUVECs to B. fragilis outer membrane fractions, separated from other components of the B. fragilis cell wall by isopycnic, sucrose gradient centrifugation, significantly increased surface expression of E-selectin and induced functional endothelial cell-dependent leukocyte adhesion. B. fragilis outer membranes induced translocation of NF-kappa B to HUVEC nuclei and accumulation of E-selectin mRNA in HUVEC cytoplasm. E-selectin expression induced by B. fragilis outer membranes was not blocked by polymixin B. In contrast, E-selectin expression induced by outer membrane fractions purified from E. coli was competitively inhibited by polymixin B. Neither purified B. fragilis LPS, a prominent constituent of the outer membrane, nor purified B. fragilis capsular polysaccharides induced HUVEC activation. Two different monoclonal antibodies directed against human CD14 completely inhibited B. fragilis outer membrane-induced NF-kappa B activation, E-selectin transcription, and E-selectin surface expression. We conclude that the outer membrane component of the B. fragilis cell wall contains a proinflammatory factor(s), that is not LPS, which induces human endothelial cell activation by a soluble CD14-dependent mechanism.
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PMID:CD14-dependent activation of human endothelial cells by Bacteroides fragilis outer membrane. 958 47

Resting membrane potential (RMP) and whole cell currents were recorded in human THP-1 monocytes adherent to polystyrene, unstimulated human umbilical vein endothelial cells (HUVECs), lipopolysaccharide (LPS)-treated HUVECs, immobilized E-selectin, or vascular cell adhesion molecule 1 (VCAM-1) using the patch-clamp technique. RMP after 5 h on polystyrene was -24.3 +/- 1.7 mV (n = 42) with delayed rectifier K+ (Idr) and Cl- currents (ICl) present in >75% of the cells. Inwardly rectifying K+ currents (Iir) were present in only 14% of THP-1 cells. Adherence to unstimulated HUVECs or E-selectin for 5 h had no effect on Iir or ICl but decreased Idr. Five hours after adherence to LPS-treated HUVECs, outward currents were unchanged, but Iir was present in 81% of THP-1 cells. A twofold increase in Iir and a hyperpolarization (-41.3 +/- 3.7 mV, n = 16) were abolished by pretreatment of THP-1 cells with cycloheximide, a protein synthesis inhibitor, or herbimycin A, a tyrosine kinase inhibitor, or by pretreatment of the LPS-treated HUVECs with anti-VCAM-1. Only a brief (15-min) interaction between THP-1 cells and LPS-treated HUVECs was required to induce Iir expression 5 h later. THP-1 cells adherent to VCAM-1 exhibited similar conductances to cells adherent to LPS-treated HUVECs. Thus engagement of specific integrins results in selective modulation of different K+ conductances.
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PMID:Modulation of K+ currents in monocytes by VCAM-1 and E-selectin on activated human endothelium. 968 58

We examined the tissue distribution of adhesion molecule gene expression in mice treated intravenously with interleukin (IL)-1 beta. E-selectin mRNA expression was selectively induced in the heart by IL-1 beta, but only slight or no induction was observed in other organs. On the other hand, intercellular adhesion molecule-1 mRNA expression was inducible in all organs examined, although it showed the strongest induction in the lung and the weakest responses in the brain and skin. Vascular cell adhesion molecule-1 mRNA was also inducible in all organs with the exception of the skin, but it was induced most markedly in the lung and the heart. The accessibility of IL-1 beta to the heart was less than that to other organs except the brain. Similar tissue-specific induction of these mRNAs was also seen when tumor necrosis factor (TNF)-alpha or lipopolysaccharide was substituted for IL-1 beta. Analysis of E-selectin mRNA expression in the heart by in situ hybridization indicated that expression was most prominent in microvascular endothelial cells and some other stromal cells, but this transcript was not seen in the lung. Although intercellular adhesion molecule-1 mRNA expression was restricted to the endothelium lining the capillaries and small arteries in the heart, its distribution in the lung covered not only the endothelium but also the cells composing the alveolar septa. In contrast, vascular cell adhesion molecule-1 mRNA expression was most prominent in endothelial cells of larger vessels in both the heart and the lung. Our results demonstrate that expression of adhesion molecules is tissue- and cell type-specific and that endothelial cells differentially express adhesion molecules depending on the size of the blood vessels.
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PMID:Interleukin-1beta induces tissue- and cell type-specific expression of adhesion molecules in vivo. 971 37

Previous studies have shown that polymorphonuclear leukocyte (PMN) adherence to endothelial cells (EC) induces transient increases in EC cytosolic free calcium concentration ([Ca2+]i) that are required for PMN transit across the EC barrier (Huang, A.J., J.E. Manning, T. M. Bandak, M.C. Ratau, K.R. Hanser, and S.C. Silverstein. 1993. J. Cell Biol. 120:1371-1380). To determine whether stimulation of [Ca2+]i changes in EC by leukocytes was induced by the same molecules that mediate leukocyte adherence to EC, [Ca2+]i was measured in Fura2-loaded human EC monolayers. Expression of adhesion molecules by EC was induced by a pretreatment of the cells with histamine or with Escherichia coli lipopolysaccharide (LPS), and [Ca2+]i was measured in single EC after the addition of mAbs directed against the EC adhesion proteins P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or platelet/endothelial cell adhesion molecule-1 (PECAM-1). Both anti-P- and anti-E-selectin mAb, as well as anti-VCAM-1 mAb, induced transient increases in EC [Ca2+]i that were comparable to those induced by 200 microM histamine. In contrast, no effect was obtained by mAbs directed against the endothelial ICAM-1 or PECAM-1. PMN adherence directly stimulated increases in [Ca2+]i in histamine- or LPS-treated EC. mAbs directed against leukocyte CD18 or PECAM-1, the leukocyte counter-receptors for endothelial ICAM-1 and PECAM-1, respectively, did not inhibit PMN-induced EC activation. In contrast, mAb directed against sialyl Lewis x (sLex), a PMN ligand for endothelial P- and E-selectin, completely inhibited EC stimulation by adherent PMN. Changes in EC [Ca2+]i were also observed after adherence of peripheral blood monocytes to EC treated with LPS for 5 or 24 h. In these experiments, the combined addition of mAbs to sLex and VLA-4, the leukocyte counter-receptor for endothelial VCAM-1, inhibited [Ca2+]i changes in the 5 h-treated EC, whereas the anti-VLA-4 mAb alone was sufficient to inhibit [Ca2+]i changes in the 24 h-treated EC. Again, no inhibitory effect was observed with an anti-CD18 or anti-PECAM-1 mAb. Of note, the conditions that induced changes in EC [Ca2+]i, i.e. , mAbs directed against endothelial selectins or VCAM-1, and PMN or monocyte adhesion to EC via selectins or VCAM-1, but not via ICAM-1 or PECAM-1, also induced a rearrangement of EC cytoskeletal microfilaments from a circumferential ring to stress fibers. We conclude that, in addition to their role as adhesion receptors, endothelial selectins and VCAM-1 mediate endothelial stimulation by adhering leukocytes.
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PMID:Endothelial cell E- and P-selectin and vascular cell adhesion molecule-1 function as signaling receptors. 973 97

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