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 role that pleural mesothelial cells play in leucocyte transmigration into the pleural cavity was investigated in lipopolysaccharide-stimulated mice. Changes in mesothelial cell morphology and changes in expression of adhesion molecules on mesothelial cells and leucocytes were analysed by light microscopy, immunohistochemistry, transmission electron microscopy (TEM) and immuno-scanning electron microscopy (immuno-SEM). After stimulation, the mesothelial cells separated completely from one another before leucocyte penetration across the mesothelial layer occurred. These changes occurred primarily in the immediate vicinity of ribs, where a large number of leucocytes accumulated. Immuno-SEM showed that the expression of intercellular adhesion molecule-1 (ICAM-1) on the parietal pleural mesothelial cells was significantly up-regulated by lipopolysaccharide stimulation, and that of vascular cell adhesion molecule-1 (VCAM-1) was induced. Both were restricted to the microvilli of the mesothelial cells. By contrast, expression of intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), peripheral node addressin (PNAd) and fibronectin were not detected. Lymphocyte function associated antigen-1 (LFA-1), macrophage-1 molecule (Mac-1) and very late appearing antigen-4 (VLA-4), all ligands of ICAM-1 and VCAM-1, were present on the transmigrated neutrophils and macrophages. These findings demonstrate that the immediate vicinity of ribs is a source of leucocyte migration into the pleural space.
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PMID:Morphological analysis of leucocyte transmigration in the pleural cavity. 1462 Mar 79

By enriching a random transposon insertion bank of Pseudomonas fluorescens for mutants affected in their adherence to the human extracellular matrix protein fibronectin, we isolated 23 adherence minus mutants. Mutants showed a defect in their ability to develop a biofilm on an abiotic surface and were impaired for virulence when tested in an in vivo virulence model in the fruit fly, Drosophila melanogaster. Molecular characterisation of these mutants showed that the transposon insertions localised to two distinct chromosomal locations, which were subsequently cloned and characterised from two mutants. A search in the databanks identified two loci in the Pseudomonas aeruginosa PAO1 genome with significant homology to the genes interrupted by the transposon insertions. Mutant IVC6 shows homology to gmd, coding for the enzyme GDP-mannose dehydratase, involved in the synthesis of A-band- O-antigen-containing lipopolysaccharide (LPS). Mutant IVG7 is significantly similar to a probable outer membrane protein of strain PAO1, with no specific function attributed thus far, yet with significant homology to Escherichia coli FadL, involved in long-chain fatty acid transport. We propose that this protein, together with LPS, is involved in the first steps of P. fluorescens adherence leading to host colonisation. Results presented here also demonstrate the pathogenic potential of P. fluorescens, assessed in an in vivo Drosophila model system, correlated with its ability to adhere to the human extracellular matrix protein, fibronectin. Correlation between the mutant phenotypes with identified virulence factors and their actual role in the virulence of P. fluorescens is discussed.
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PMID:In vitro identification of two adherence factors required for in vivo virulence of Pseudomonas fluorescens. 1462 13

Migration of dendritic cells (DC) from sentinel sites to lymphoid tissue entails the initiation and coordination of a complex series of cytoskeletal rearrangements resulting in polarised protrusion, formation of new adhesion points, and detachment. Although many diverse receptor-ligand interactions stimulating DC maturation and migration have been identified, the changes that occur in the structure of the actin cytoskeleton during these processes have received little attention. When derived in vitro, immature DC floated in clumps, and upon addition of maturation stimuli such as lipopolysaccharide (LPS), they rapidly adhered, developed polarity, and assembled actin-rich structures known as podosomes at the leading edge of the cell. Podosome assembly was associated with the specific recruitment of beta2 integrins, which in the absence of the Wiskott Aldrich Syndrome protein (WASp), did not occur. As maturation progressed, normal DC once again became rounded and devoid of podosomes. This change in morphology was closely associated with a quantitatively reduced ability to adhere to fibronectin or ICAM-1-coated surfaces. In immature DC, failure to form podosomes or selective inhibition of the CD18 component of podosomes resulted in a similarly reduced ability to adhere to ICAM-1, indicating that podosomes, through CD18, are necessary for tight adhesion to this ligand. We, therefore, propose that podosomes provide an essential link between directional cell protrusion and achievement of DC translocation by establishing new dynamic anchor points at the front of the cell. The temporal regulation of podosome assembly during DC maturation also suggests that they may be most critical for early movement, perhaps during transmigration of lymphatic endothelium.
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PMID:Maturation of DC is associated with changes in motile characteristics and adherence. 1469 51

Over the last decade a vast amount of reports have shown that galectin-1 and galectin-3 are important mediators of inflammation. In this review we describe how the galectins may be involved in several parts of the inflammatory process, including the recruitment of neutrophils into an infected tissue and the recognition and killing of bacteria by activation of the tissue destructive phagocytic respiratory burst. During bacterial infection or aseptic inflammatory processes, galectins are produced and released by e.g. infected epithelium, activated tissue-resident macrophages and endothelial cells. These extracellular galectins may facilitate binding of neutrophils to the endothelium by cross-linking carbohydrates on the respective cells. Further the galectins improve binding of the neutrophil to the extracellular matrix proteins laminin and fibronectin, and are potential chemotactic factors, inducing migration through the extracellular matrix towards the inflammatory focus. When the cells encounter bacteria, galectin-3 could function as an opsonin, cross-linking bacterial lipopolysaccharide or other carbohydrate-containing surface structures to phagocyte surface glycoconjugates. Both galectin-1 and galectin-3 have the capacity to induce a respiratory burst in neutrophils, provided that the cells have been primed by degranulation and receptor upregulation. The reactive oxygen species produced may be destructive to the invading micro-organisms as well as to the surrounding host tissue, pointing out the possible role of galectins, not only in defence toward infection, but also in inflammatory-induced tissue destruction.
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PMID:Galectins as inflammatory mediators. 1475 82

Although the interleukin (IL)-1 receptor is densely distributed in the leptomeninges constituting the blood/cerebrospinal fluid barrier, its physiologic significance has remained unclear. In the present study, we show that in cultured leptomeningeal cells, IL-1beta, tumor necrosis factors, or lipopolysaccharide causes a prominent increase in the synthesis and release of prostaglandin (PG) D synthase, which catalyzes the final step in the biosynthesis of PGD2. Although significant increases in the amount of PGD synthase were also observed with cells exposed to somatostatin, thrombin, or ciliary neurotrophic factor, these were much smaller than were those induced by the proinflammatory cytokines. Other agents tested including IGF-I had no effect upon the enzyme levels in the culture media. Furthermore, we found that the increased secretion of PGD synthase by IL-1beta was completely inhibited by 10(-7) M PGE2. The same dose of PGD2 or 15-deoxy-Delta(12-14)PGJ2 had no effect upon the IL-1beta action. In addition, PGE2 increased the level of fibronectin and eliminated the expression of zonula occludentes-1, a tight junction-associated protein from cultured cells, effects likely reflecting a loss of barrier integrity. These results demonstrate the importance of inflammatory stimuli as a physiologic regulator of the leptomeningeal cell function.
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PMID:Effects of interleukin-1beta and prostaglandin E2 on prostaglandin D synthase production in cultivated rat leptomeningeal cells. 1508 10

Interaction of tumor cells with the vascular wall is required for metastasis from the bloodstream. The precise interaction among metastatic cells, circulating platelets, the vessel wall, and physiological flow conditions remains to be determined. In this study, we investigated the interaction of shear on metastatic cell lines adherent to lipopolysaccharide (LPS)-treated endothelium. Tumor cells were perfused over LPS-treated human umbilical vein endothelial cells (HUVECs) at incremental venous shear rates from 50 to 800 s(-1). At a venous shear rate of 400 s(-1), 3% of adherent tumor cells formed pseudopodia under shear, a process we termed shear-induced activation. Because platelets promote tumor dissemination, we then investigated the effect of pretreating tumor cells with platelet releasate collected from activated platelet concentrate. We found that in the presence of platelet releasate, the number of tumor cells adhering to HUVECs increased and tumor "activation" occurred at a significantly lower shear rate of 50 s(-1). This was inhibited with acetylsalicylic acid. Depletion of fibronectin or vitronectin from the platelet releasate resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s(-1). The integrin alphavbeta3 has been shown to mediate cell adhesion primarily through vitronectin and fibronectin proteins. Inhibition of alphavbeta3, followed by the addition of platelet releasate to the tumor cells, resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s(-1). Collectively, our data suggest that alphavbeta3 promotes the metastatic phenotype of tumor cells through interactions with the secreted platelet proteins vitronectin and fibronectin under venous shear conditions.
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PMID:Shear stress modulates the interaction of platelet-secreted matrix proteins with tumor cells through the integrin alphavbeta3. 1524 Mar 42

Cell adhesion, cell growth and cell activities of macrophages and fibroblasts, cultured on newly developed degradable multiblock-copolyesters were studied to examine the biocompatibility and the possible use of these polymers for medical applications. The biocompatibility and the biodegradability of the polymers were confirmed by subcutaneous implantation of polymer foils in rats. The newly developed polymers, two polyesters (DegraPol/bsc43 and DegraPol/bsd43) and a polyesterether (DegraPol/bst41), were found to exhibit good cell compatibility; the cell-to-substrate interactions induced neither cytotoxic effects nor activation of macrophages. The adhesion and growth of fibroblasts and macrophages were different among the substrate. Fibroblasts adhered on the polyesters to about 60% of control cell cultured on tissue culture polystyrene (TCPS) and proliferated in the same doubling time as on TCPS. On the polyetherester cells exhibited weak adhesion; however, they proliferated up to day 4 after plating at the same doubling time as on TCPS (of about 42 h), and then decreased their doubling time to 27 h. Macrophages attached to the polyesters to about 40-60% of TCPS but no significant change was seen in the doubling time of cells cultured on TCPS and the polyesters. Again on the polyetherester, macrophages exhibited relatively low adhesion (25% of TCPS) and high doubling time (about 100 h). Fibroblasts produced high amounts (up to 500% of control cells) of collagen type I and type IV, and fibronectin. Macrophages responded to lipopolysaccharide treatment by the production of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha), indicating that the cell-to-polymer interactions allow fibroblasts and macrophages to maintain their phenotype. All three test polymers exhibit favourable tissue compatibility. The formed capsule was just a few cell layers thick (<30 microm). After 2 months implanted subcutaneously in rats, the molecular weight of the test polymers was reduced by >20% depending on their chemical structure. Taken collectively, the present data demonstrate that the newly developed multiblock copolyesters are biocompatible and biodegradable.
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PMID:Multiblock copolyesters as biomaterials: in vitro biocompatibility testing. 1534 17

Regulated migration and spatial localization of dendritic cells (DCs) are critical events during the initiation of physiologic immune responses and maintenance of tolerance. Here we have used cells deficient in the Wiskott-Aldrich syndrome protein (WASp) to demonstrate the importance of dynamic remodeling of the actin cytoskeleton for these trafficking processes to occur in vitro and in vivo. On fibronectin-coated surfaces, WASp-null immature murine DCs exhibited defects both of attachment and detachment, resulting in impaired net translocation compared with normal cells. The chemokinetic response to CCL21, which is critical for normal lymphatic trafficking, was also abrogated in the absence of WASp. In vivo in both fluorescein isothiocyanate (FITC) and oxazolone contact hypersensitivity models, WASp-null Langerhans cell (LC) migration was compromised, as judged by exit from the skin as well as by homing to the draining lymph node (LN). Furthermore, following systemic challenge with lipopolysaccharide (LPS) or toxoplasma-derived antigen, WASp-null DCs showed incomplete redistribution to T-cell areas in the spleen. Instead, they were retained ectopically in the marginal zone. DC trafficking in vivo is therefore dependent on a normally regulated actin cytoskeleton, which performs an essential function during maintenance of physiologic immunity and when disturbed may contribute significantly to the immunopathology of Wiskott-Aldrich Syndrome.
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PMID:Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein. 1549 25

Multiple-organ failure related to septicemia is a common cause of early mortality after liver transplantation. Endotoxemia following living donor hepatectomy may be a cause of postoperative death. Plasma fibronectin (Fn) exerts a broad range of biological effects on cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, reticuloendothelial system function, and ischemic injury. We studied the therapeutic effect of plasma Fn in mice after an intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (GalN). Female Balb/c mice received simultaneous intraperitoneal injection of LPS (50 microg/kg) and GalN (400 mg/kg). Thirty minutes prior to GalN/LPS administration, plasma Fn or bovine serum albumin was given intravenously. A single administration of plasma Fn (500 mg/kg) protected in dose-dependent fashion against lethal shock after GalN/LPS challenge. Plasma Fn significantly reduced the serum tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 levels and significantly increased the serum interleukin-10 levels after GalN/LPS administration. Furthermore, plasma Fn significantly inhibited liver necrosis at 9 hours after GalN/LPS injection. The fraction of apoptotic-positive cells in these plasma Fn-treated mice was significantly lower than in the control group. These results support the protective treatment of endotoxin-induced liver injury by plasma Fn.
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PMID:Fibronectin suppresses apoptosis and protects mice from endotoxic shock. 1556 Dec 70

This study was undertaken to clarify the mechanisms by which C-fiber degeneration at neonatal stages exacerbates the inflammatory responses of rat airways. Rats were treated with capsaicin at neonatal stages and immunized with ovalbumin (OVA) at adult ages. Challenge of capsaicin-pretreated rats with OVA promoted a higher influx of neutrophils in bronchoalveolar lavage (BAL) fluid compared with the vehicle group. No significant differences were found for the other cell types. The increased adhesion of N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1 microM)- and phorbol myristate acetate (PMA; 1 microM)-treated neutrophils to fibronectin-coated wells did not differ among vehicle- and capsaicin-pretreated rats. Additionally, fMLP (10 microM), platelet-activating factor (0.1 microM), and substance P (50 microM) induced a significant neutrophil chemotaxis, but no differences were found among vehicle and capsaicin groups. Increased levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and leukotriene B4 in BAL fluid as well as higher expression of cytokine-induced neutrophil chemoattractant (CINC)-3 in lung homogenates were detected in the capsaicin group compared with vehicle group. In the capsaicin group, chronic treatment with compound 48/80 restored the TNF-alpha levels to control values and prevented the neutrophil influx in BAL fluid. The enhanced production of TNF-alpha, superoxide anion, and nitrite by isolated alveolar macrophages in response to lipopolysaccharide (3 microg/ml), PMA (10 nM), and/or zymosan (100 particles/cell) did not differ between vehicle- and capsaicin-pretreated rats. In conclusion, chronic neuropeptide depletion promoted by neonatal capsaicin treatment up-regulates airways mast cells, which upon activation by antigen at adult ages, release large amounts of cytokines such as TNF-alpha and CINC-3 that accounts for the massive airways neutrophil infiltration.
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PMID:Mechanisms involved in the enhancement of allergic airways neutrophil influx by permanent C-fiber degeneration in rats. 1557 95


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