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

The prerequisites for the initiation of pathophysiological effects of endotoxin (lipopolysaccharide [LPS]) include binding to and possibly internalization by target cells. Monocytes/macrophages are prominent target cells which are activated by LPS to release various pro- and anti-inflammatory mediators. The aim of the present study was to establish a new method to determine the binding and internalization rate of different LPS chemotypes by human monocytes and to correlate these phenomena with biological activity. It was found that membrane-bound LPS disappears within hours from the surface being internalized into the cell. Further, a correlation between the kinetics of internalization and the length of the sugar chain as well as an inverse correlation between the time course of internalization and LPS hydrophobicity was revealed. Comparison of the internalization kinetics of different LPS chemotypes with kinetics of tumor necrosis factor alpha release and kinetics of oxidative burst did not reveal any correlation of these parameters. These findings suggest that cellular internalization of and activation by LPS are mechanisms which are independently regulated.
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PMID:The internalization time course of a given lipopolysaccharide chemotype does not correspond to its activation kinetics in monocytes. 1022 15

Coagulation is initiated on tissue-factor-bearing cells when factor VIIa complexes with membrane-bound tissue factor and activates factors X and IX. Cellular tissue factor activity does not correlate with tissue factor antigen; treatment with calcium ionophore rapidly increases tissue factor activity without increasing tissue factor antigen. Our study examined the effect of calcium ionophore A23187 on tissue factor activity of freshly isolated, lipopolysaccharide-stimulated monocytes and non-transformed human dermal fibroblasts. A23187 increased tissue factor activity on monocytes and fibroblasts in a dose-dependent fashion between 0.1 and 50 micromol/l ionophore. This increase in activity was proportional to an increase in intracellular calcium in monocytes. The increase in tissue factor activity was partially attributable to an increase in phosphatidylserine expression, as measured by increased prothrombinase activity (1.1- to 4-fold) on ionophore-treated cells. The phosphatidylserine-binding protein annexin V decreased tissue factor activity on both ionophore-treated and untreated cells, reflecting the role of phosphatidylserine in tissue factor activity. However, even in the presence of saturating concentrations of annexin V, the tissue factor activity of ionophore-treated cells was 1.3- to 11.3-fold higher than that of untreated cells, indicating that the increase in tissue factor activity did not result solely from increased expression of phosphatidylserine. A23187 increased tissue-factor-dependent activation of factors IX and X 1.4- to 7-fold on both cell types, indicating that ionophore treatment did not alter factor VIIa/tissue factor substrate specificity. We conclude that the mechanism by which calcium ionophore increases tissue factor activity is not unique to monocytoid or transformed cells. Furthermore, the ionophore-induced increase in activity is not solely the result of increased exposure to phosphatidylserine. Finally, tissue factor de-encryption by A23187 does not alter factor VIIa/tissue factor substrate specificity.
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PMID:Tissue factor de-encryption: ionophore treatment induces changes in tissue factor activity by phosphatidylserine-dependent and -independent mechanisms. 1039 Jan 20

The morphology of membrane-bound intracellular inclusions, or 'cysts', of epitheliocystis from sea bream Sparus aurata is described. Inclusions under the light microscope appear either granular or amorphous. Granular inclusions do not elicit a proliferative host reaction and contain the 3 distinctive developmental stages of chlamydial organisms: the highly pleomorphic reproductive form or reticulate body, the condensing form or intermediate body and the infective non-dividing rather uniform elementary body. Amorphous inclusions may elicit a proliferative host reaction and contain prokaryotic organisms which differ morphologically from those reported within granular cysts. More or less elongated electron-lucent organisms divide by fission to give rise to electron-dense non-dividing small cells with a dense nucleoid. Vacuolated and non-vacuolated small cells are reported. The morphology and developmental cycle of sea bream epitheliocystis agents would support their chlamydial nature; however, the immunohistochemical study conducted on gill samples which carried both inclusions failed to demonstrate the expression of lipopolysaccharide (LPS) chlamydial antigen. The different stages of the 2 distinct developmental cycles described in the present study are compared with electron microscope observations of epitheliocystis organisms reported from different host species. The hypothesis that epitheliocystis infection in the sea bream might be caused by a unique highly pleomorphic chlamydia-like agent, the life history of which includes 2 entirely different developmental cycles, is discussed.
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PMID:Epitheliocystis agents in sea bream Sparus aurata: morphological evidence for two distinct chlamydia-like developmental cycles. 1043 4

The lone CX3C chemokine, fractalkine (FK), is expressed in a membrane-bound form on activated endothelial cells and mediates attachment and firm adhesion of T cells, monocytes and NK cells. We now show that FK is associated with dendritic cells (DC) in epidermis and lymphoid organs. In normal human skin, dual-color fluorescence microscopy co-localized FK expression with Langerhans cells expressing CD1a. In tonsil, FK-positive DC expressed CD83, a marker for mature DC. Human and murine cultured DC up-regulated FK mRNA expression with maturation. Furthermore, CD40 ligation, but not TNF-alpha or lipopolysaccharide treatment, of activated, migratory DC that had migrated from skin explants resulted in a 2.5-fold increase of surface expression of FK without significant alterations of expression of CD80, CD86, CD54 or MHC class II. Since FK mediates adhesion of T cells to activated endothelial cells, the increased expression of FK during DC maturation (and particularly by CD40 ligation) may play a role in the ability of T cells and mature DC to form conjugates and engage in cell-cell communication.
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PMID:Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation. 1045 70

Tumour necrosis factor-alpha (TNF-alpha), secreted by cells of the macrophage-monocyte lineage, has a well established role in inflammation and host-defence. The more recent discovery that adipocytes also secrete TNF-alpha has led to a substantial body of research implicating this molecule in the insulin resistance of obesity. However, little is known about the normal regulation of TNF-alpha release from human adipose tissue. In particular, it is not known whether adipocyte production of TNF-alpha is responsive to similar or different molecular regulators than those relevant to macrophages. TNF-alpha release from cultured human adipose tissue and isolated adipocytes was examined using an ELISA. Insulin, cortisol or the thiazolidinedione, BRL 49653, did not have a significant effect on TNF-alpha release from adipose tissue or isolated adipocytes. In contrast, lipopolysaccharide (LPS), a major stimulus of TNF-alpha protein production in monocytes and macrophages, resulted in a fivefold stimulation of TNF-alpha release from human adipose tissue. Significant stimulation of TNF-alpha release was also seen from isolated adipocytes, indicating that the increase in TNF-alpha release from adipose tissue in the presence of LPS is unlikely to be entirely attributable to contaminating monocytes or macrophages. Consistent with this observation was the finding that mRNA for CD14, a known cellular receptor for LPS, is expressed in human adipocytes. The increase in TNF-alpha protein release in response to LPS was blocked by an inhibitor of the matrix metalloproteinase responsible for the cleavage of the membrane-bound proform of TNF-alpha, indicating that this release represented regulated secretion and was not due to cell lysis. In conclusion, the regulation of TNF-alpha protein release from human adipose tissue and isolated adipocytes appears to be similar to its regulation in cell types more traditionally implicated in host defence. The production by the adipocyte of a range of molecules involved in host defence-TNF-alpha, factors D, B and C3, interleukin-6, and macrophage colony-stimulating factor--suggest that this cell type may make a significant contribution to innate immunity.
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PMID:Regulation of tumour necrosis factor-alpha release from human adipose tissue in vitro. 1049 4

Macrophage activation and deactivation play essential roles in the initiation and maintenance of a successful immune response. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP), two structurally related neuropeptides, act as macrophage deactivating factors. We reported previously that VIP and PACAP inhibit IL-6, IL-12, TNF alpha and NO production, and enhance IL-10 production, from lipopolysaccharide (LPS)-stimulated macrophages. In this study, we demonstrate that VIP and PACAP down-regulate the expression of CD14, the membrane-bound LPS receptor, by inducing its rapid shedding. The soluble CD14 released by VIP and PACAP corresponds in size to the soluble CD14 released by PMA. Neither VIP/PACAP nor PMA, affect the steady-state levels of CD14 mRNA. The CD14 shedding induced by VIP/PACAP is mediated through the PAC1 specific receptors and the major transduction pathway involves the protein kinase C (PKC). The VIP/PACAP inhibition of TNF alpha and NO occurs through both CD14-dependent and -independent mechanisms, whereas the inhibition of IL-6 production appears to be strictly CD14-dependent. The shedding of CD14 by VIP and PACAP represents an important mechanism by which these neuropeptides limit the macrophage inflammatory response.
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PMID:Shedding of membrane-bound CD14 from lipopolysaccharide-stimulated macrophages by vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide. 1049 78

Tumor necrosis factor-alpha (TNF-alpha) is released from the cell surface by cleavage of pro-TNF-alpha by metalloproteinases (MPs). In cell cultures, inhibition of MPs has been found not only to reduce the release of TNF-alpha, but also to enhance the surface expression of TNF-alpha and TNF-alpha receptors, which might lead to a proinflammatory effect. To determine the effect of MP inhibition during inflammation in humans, 7 healthy subjects were studied after intravenous injection of lipopolysaccharide (LPS; 4 ng/kg) preceded (-20 minutes) by an oral dose of the MP inhibitor GI5402 (100 mg) or matching placebo. GI5402 strongly reduced LPS-induced TNF-alpha release (P <.001), but did not influence the increase in monocyte-bound TNF-alpha. In addition, GI5402 attenuated the rise in plasma-soluble TNF-alpha receptors types I and II after LPS injection (both P <.001), but did not change the LPS-induced decreases in granulocyte and monocyte TNF-alpha receptor expression. These data suggest that MP inhibitors may be useful as a treatment modality in diseases in which excessive production of TNF-alpha is considered to play an important role. Furthermore, unlike in vitro, no evidence has been found in vivo with MP inhibition for a potential proinflammatory effect due to increases in membrane-bound TNF-alpha and TNF-alpha receptor number.
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PMID:The effect of a metalloproteinase inhibitor (GI5402) on tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha receptors during human endotoxemia. 1049 96

The enzyme sialyltransferase (STase) of Neisseria gonorrhoeae is a major pathogenicitiy determinant. Using a refined method for assaying the STase activity, the Km for CMP-NANA was shown to be 14 +/- 2 microM, higher than that reported previously. Rates of sialylation by Nonidet extracts, prepared under conditions that optimise solubilisation of the membrane-bound enzyme, were 6 to 20 nmol of NANA transferred from CMP-14C-NANA onto isolated lipopolysaccharide/min./mg of extracted protein, far higher than the previously reported rates of less than 1 nmol of NANA transferred/min./mg of extracted protein. Gonococci grew more slowly with lactate or pyruvate than with glucose as the carbon source. Although growth with a mixture of limiting concentrations of both glucose and lactate was biphasic, diauxic growth was also found in the control culture supplied with glucose alone. The growth rate in the presence of lactate alone was slower than with glucose. The growth rate increased slightly relative to the glucose culture when both substrates were available; lactate was consumed more rapidly than glucose. Higher STase activities were found in bacteria harvested in the exponential than in the stationary phase of aerobic growth: the activity in aerated cultures was higher than those of oxygen-limited or anaerobic cultures. Similar STase activities were found in bacteria that had been grown with glucose, lactate or pyruvate as the carbon and energy source. Sialyltransferase synthesis is essentially constitutive: it is not regulated by glucose repression or by induction by lactate or anaerobiosis.
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PMID:Regulation of the lipopolysaccharide-specific sialyltransferase activity of gonococci by the growth state of the bacteria, but not by carbon source, catabolite repression or oxygen supply. 1051 Jul 25

Human monocyte-derived dendritic cells (DC) use mannose receptor (MR)-mediated endocytosis for efficient antigen capture and targeting to the endosomal/lysosomal compartment. Active biosynthesis of the MR takes place in such cells. We now report that a substantial percentage (up to 20%) of these newly synthesized MR are secreted into the culture medium. The secretion of the soluble MR (sMR) was found to be proportional to the rate of synthesis. The addition of the inflammatory mediator lipopolysaccharide (LPS) to DC, known to induce maturation, strongly reduced MR synthesis, expression and shedding of the MR. The sMR is approximately 10 kDa smaller than the membrane-bound form, but contains an intact N-terminus, indicating the lack of the cytoplasmic and transmembrane region. The sMR appeared to be directly generated from the cell-bound form, indicative of proteolytic cleavage. Importantly, the sMR has maintained its mannose-binding properties since it was capable of binding a mannosylated ligand. The high amount of sMR released by DC and its ability to bind mannosylated ligand might indicate that this molecule plays a role in the transport of mannosylated proteins from the site of inflammation to other parts of the body. Whether that contributes to the generation of immune responses remains to be determined.
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PMID:Human dendritic cells shed a functional, soluble form of the mannose receptor. 1054 81

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a widely expressed EGF superfamily member that induces mitogenic and/or chemotactic activities toward different cell types through binding to EGF receptors 1 or 4. Membrane-bound HB-EGF exerts growth activity and adhesion capabilities and possesses the unique property of being the receptor for diphtheria toxin (DT). Using molecular and functional techniques, we show that human polymorphonuclear granulocytes (PMN), which did not express HB-EGF in resting conditions, expressed it at mRNA and protein level, following incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF). Other classic agonists for PMN (including lipopolysaccharide, phagocytable particles, tumor necrosis factor-alpha, or G-CSF) failed to induce HB-EGF. The effects of GM-CSF on HB-EGF mRNA levels were concentration-dependent, reached a plateau after 1 to 2 hours of stimulation, and did not require protein synthesis. After GM-CSF treatment, membrane-bound HB-EGF was detected by flow cytometry. At the same time, PMN acquired sensitivity to the apoptosis-promoting effect of DT, which, moreover, specifically suppressed the GM-CSF-induced priming of formyl-methionyl-leucyl-phenylalanine-stimulated superoxide anion release. Finally, soluble HB-EGF was detected in the PMN culture medium by a specific enzyme-linked immunosorbent assay. Thus, we provide evidence that HB-EGF is specifically inducible by GM-CSF in PMN and represents a novel peptide to be included in the repertoire of PMN-derived cytokines.
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PMID:Granulocyte-macrophage colony-stimulating factor induces expression of heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor and sensitivity to diphtheria toxin in human neutrophils. 1055 4


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