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

Polymorphonuclear neutrophil (PMN) accumulation within damaged tissues, a hallmark of acute inflammation, is dependent upon initial adhesion to endothelial cells. In vitro studies suggest that P-selectin and platelet activating factor (PAF) are key molecules in this process by promoting the initial adhesion of PMN to endothelial cells. We report in vivo studies in which intravenous administration of lipopolysaccharide (LPS) to anesthetized rats caused a very rapid onset (< 5 min) of neutropenia, in association with induction of surface expression of P-selectin on microvascular endothelial cells in kidney, liver and lung; analogous induction of P-selectin expression by cultured endothelial cells was observed in response to LPS stimulation in vitro. In addition, treatment with an antibody (Ab) to P-selectin (or use of a PAF antagonist) blocked development of neutropenia in vivo for at least 15 min post-LPS injection, and Ab treatment was shown to block PMN accumulation in tissues. These studies document roles for P-selectin and PAF in the early adhesion of PMN to endothelial cells in vivo.
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PMID:P-selectin and platelet-activating factor mediate initial endotoxin-induced neutropenia. 750 2

We have cloned the cDNA encoding rat P-selectin (Psel) and have examined the regulation of Psel expression in vivo. Sequence analysis of the complete Psel cDNA demonstrated significant nucleotide and amino-acid identity with human and mouse Psel. Similar to mouse Psel, the rat sequence lacks the equivalent of human complement regulatory protein-like repeat 2 (CR2). Seven potential N-linked glycosylation sites are conserved between the three species, suggesting that carbohydrate modification may play an important role in Psel function. To examine expression of Psel in vivo, levels of Psel mRNA were examined in several different tissues after systemic administration of lipopolysaccharide (LPS). Psel mRNA was undetectable in tissues of vehicle-treated animals. By 3 after LPS administration, Psel mRNA levels were elevated in all tissues examined, the highest levels being seen in the lung. Significant increases in Psel mRNA were also seen in the heart, thymus, spleen and kidney. By 24 h after LPS, mRNA levels for Psel remained elevated in the lung, heart, kidney, thymus and small intestine. Psel mRNA was not detectable in total RNA isolated from purified rat platelets, suggesting that the increased levels of Psel mRNA were the result of upregulation of endothelial gene expression. In addition, only minimal levels of platelet factor 4 mRNA (PF4), used as a platelet-specific marker, were observed in the tissues studied. These data demonstrate that part of the response to acute inflammation in vivo includes the rapid increase in endothelial Psel expression.
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PMID:Cloning, sequence comparison and in vivo expression of the gene encoding rat P-selectin. 752 13

Prior to extravasation at sites of acute inflammation, neutrophils roll over activated endothelium. Neutrophil rolling is often characterized by the average rolling velocity. An additional dynamic feature of rolling that has been identified but not extensively studied is the fluctuation in the rolling velocity about the average. To analyze this characteristic further, we have measured the instantaneous velocity of bovine neutrophils interacting with lipopolysaccharide-stimulated bovine aortic endothelium at shear stresses of 1, 2, 3, and 4 dynes/cm2. The average velocities are quantitatively similar to those reported for human neutrophils rolling over reconstituted P-selectin at a surface density of 400 sites/microns 2. At all shear stresses tested, the population average variance in the instantaneous velocity is at least 2 orders of magnitude higher than the theoretical variance generated from experimental error, indicating that the neutrophils translate with a nonconstant velocity. Possible sources of the variance are discussed. These include "macroscopic" sources such as topological heterogeneity in the endothelium and microscopic sources, such as inherent stochastic formation and breakage of the receptor-ligand bonds that mediate the rolling. Regardless of the ultimate source of the variance, these results justify the use of mathematical models that incorporate stochastic processes to describe bond formation and breakage between the neutrophil and the endothelium and hence are able to generate variable velocity trajectories.
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PMID:Dynamics of neutrophil rolling over stimulated endothelium in vitro. 752 Dec 29

Tissue factor (TF) is the cellular receptor for factor VIIa. In complex with TF, factor VIIa initiates coagulation by activation of factor IX and factor X. TF is normally not in contact with blood, but is expressed on extravascular cells which forms a haemostatic envelope ready to activate coagulation when vascular integrity is disrupted. However, under pathological conditions monocytes, but probably not endothelial cells, are stimulated to express TF activity on the surface of the cells and may thereby trigger activation of blood coagulation. For several years we have observed some individuals (high responders) with a very high response to lipopolysaccharide (LPS) as judged by induction of TF activity in their monocytes in whole blood. This phenomenon has been shown to be mediated by a P-selectin dependent interaction between granulocytes, platelets and monocytes where the release of platelet factor 4 (PF4) plays an important role. It is concluded that cellular interactions play a central role in the expression of TF activity in circulating monocytes.
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PMID:Cellular interactions in tissue factor expression by blood monocytes. 754 63

In a previous study we have shown that granulocytes enhance lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes in a platelet-dependent reaction. The present investigation was undertaken to examine the role of a platelet activation product, platelet factor 4 (PF4), in LPS-induced TF activity in monocytes. Platelet lysate supernatant, purified PF4, and the COOH-terminal tridecapeptide of PF4, termed PF4(58-70), enhanced LPS-induced TF activity in monocytes of whole blood dose dependently. A monoclonal antibody against P-selectin eliminated the enhancing effect of PF4(58-70) on LPS-induced TF activity in monocytes, and PF4(58-70) was shown to act synergistically with tumor necrosis factor alpha (TNF-alpha). However, PF4(58-70) did not enhance TNF-alpha secretion in LPS-stimulated whole blood. The major effect of PF4(58-70) was granulocyte dependent. Our results suggest that PF4 might play an important role in LPS-stimulated monocyte TF activity of whole blood.
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PMID:A novel biological effect of platelet factor 4 (PF4): enhancement of LPS-induced tissue factor activity in monocytes. 759 59

Endothelial damage, synovial oedema, fibrin deposition, polymorphonuclear cell (PMN) invasion, and mild lining cell hyperplasia characterize acute inflammatory arthritis. Later on, perivascular tissue is infiltrated by mononuclear cells. The early events are mediated by interactions between PMNs and endothelial cells. Both parts in the adhesion event are activated with multiple stimuli resulting in complex interactions of varying intensity and duration. Adhesion molecules present on the surface of PMNs (L-selectin) or induced by inflammatory stimuli (beta 2-integrins) mediate PMN adhesion to activated endothelium, which has counter receptors (E-selectin for L-selectin and ICAM-1 and ICAM-2 for beta 2-integrins). At the initial phase L-selectin initiates the rolling of PMNs on endothelial cells. Further stimuli result in a more prolonged adhesion between PMNs and endothelium. At the side of endothelium, induction of P-selectin and PAF by histamine, thrombin and LTC4 contribute to the acute rolling of PMNs on endothelial surface. Tumor necrosis factor (TNF), interleukin-1 (IL-1) and lipopolysaccharide activate endothelial cells to synthesize interleukin-8 (IL-8), a potent chemotactic and proadhesive mediator for PMNs, and further adhesion molecule (E-selectin), a mediator of long-term adhesion between PMN and endothelium. After adhesion and migration to the focus of inflammation, PMNs induce inflammation by aggregating, releasing hydrolyzing enzymes, generating lipid peroxidation products such as prostaglandins and LTB4, and oxygen derived free radicals. In studies on the pathogenesis of seronegative spondyloarthropathies, we have shown persistently aberrant PMN function evidenced by enhanced chemotaxis and high production of toxic oxygen derived free radicals by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The present knowledge of the inflammatory process and the inflammatory mediators. 781 74

P-selectin is a Ca(2+)-dependent lectin that participates in leukocyte adhesion to vascular endothelium and platelets. Myeloid cells and a subset of T lymphocytes express carbohydrate ligands at the cell surface. Previously, we suggested that heat stable antigen (HSA/mouse CD24), an extensively glycosylated cell surface molecule on many mouse cells, is a ligand for P-selectin. Here we show that HSA mediates the binding of monocytic cells and neutrophils to P-selectin. The monocytic cell lines ESb-MP and J774, peritoneal exudate cells, and bone marrow neutrophils could bind to lipopolysaccharide-activated bend3 endothelioma cells under rotation-induced shear forces and this binding was inhibited by mAb to P-selectin and HSA. Blocking was weak at room temperature but more efficient at 4 degrees C when integrin-mediated binding was decreased. Also the adhesion of neutrophils to stimulated platelets expressing P-selectin was blocked by HSA- and P-selectin-specific mAb. Latex beads coated with purified HSA from myeloid cells bound to activated endothelioma cells or platelets, and the binding was similarly blocked by mAb to P-selectin and HSA respectively. The HSA-coated beads were stained with P-selectin-IgG, very weakly with L-selectin-IgG but not with E-selectin-IgG. The staining was dependent on divalent cations and treatment with endoglycosidase F or neuraminidase indicated that sialylated N-linked glycans were recognized. The presence of these glycans was confirmed by biosynthetic labeling studies. Our data suggest that HSA, in addition to the recently identified 160 kDa glycoprotein ligand on mouse neutrophils, belongs to a group of monospecific P-selectin ligands on myeloid cells.
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PMID:Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. 856

Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis (Frenette et at, Proc Natl Acad Sci USA 92:7450, 1995). We report here that the P-selectin--deficient mice show a 40% prolongation of the bleeding time on amputation of the tip of the tail. Moreover, defective hemostasis was observed in a local Shwartzman-like reaction induced by skin injections of lipopolysaccharide followed by tumor necrosis factor-alpha in the P-selectin--deficient mice. The hemorrhagic lesions, quantitated both macroscopically and microscopically, were twofold larger in the P-selectin--deficient mice. This was also confirmed by measuring the radioactivity in the skin using chromium-labeled red blood cells. Therefore, it is evident that P-selectin plays a role in hemostasis as suggested by its support of platelet rolling.
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PMID:Defects in hemostasis in P-selectin-deficient mice. 860 10

The role of selectins in mediating eosinophil recruitment in vivo was assessed in a model of lipopolysaccharide (LPS)-induced mouse pleurisy. LPS administration resulted in significant eosinophil influx at 24 hours, whereas neutrophil recruitment to the cavity peaked at 4 hours and persisted for 24 hours. The anti-L-selectin monoclonal antibody (MoAb) MEL-14 effectively inhibited (by 97%) eosinophil influx at 24 hours and also inhibited neutrophil recruitment at both times (75% to 95%). Eosinophil recruitment was partially reduced (54%) by the anti-P-selectin MoAb 5H1 but, in contrast, was unaffected by the anti-E-selectin MoAb 10E6. Neutrophil influx at 4 or 24 hours was not affected by the anti-P- or anti-E-selectin MoAbs. However, coadministration of anti-P-selectin and anti-E-selectin was very effective at inhibiting eosinophil influx at 24 hours (86%) and neutrophil influx at 4 (93%) and 24 hours (92%). These results show that all three selectins play a role in LPS-induced eosinophil and neutrophil recruitment in vivo, although P- and E-selectin show a degree of functional redundancy. The demonstration that P-selectin mediates eosinophil but not neutrophil influx suggests that suppressing the function of this adhesion molecule may be beneficial in blocking eosinophil accumulation in pleural inflammation.
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PMID:Selectins mediate eosinophil recruitment in vivo: a comparison with their role in neutrophil influx. 865 45

During acute inflammation, P-selectin is transiently mobilized from Weibel-Palade bodies to the surface of histamine-activated endothelial cells, where it mediates rolling adhesion of neutrophils under hydrodynamic flow. During chronic or allergic inflammation, sustained expression of P-selectin on the endothelial cell surface has been observed. We found that the cytokines interleukin 4 (IL-4) or oncostatin M (OSM) induced a five- to ninefold increase in P-selectin messenger RNA (mRNA) in human umbilical vein endothelial cells (HUVEC) that persisted as long as 72 h. IL-4 elevated P-selectin mRNA by increasing its transcription rate rather than by prolonging its already long half-life. Stimulation of P-selectin transcription by IL-4 or OSM required new protein synthesis and tyrosine phosphorylation of cellular proteins. Tumor necrosis factor alpha, IL-1 beta, lipopolysaccharide, or IL-3 did not increase P-selectin mRNA in HUVEC, and did not augment the IL-4-induced increase in P-selectin transcripts. IL-4 or OSM increased P-selectin protein on the cell surface as well as in Weibel-Palade bodies. Under flow conditions, neutrophils rolled on P-selectin expressed by IL-4-treated HUVEC, and even more neutrophils rolled on P-selectin after IL-4-treated HUVEC were stimulated with histamine. These data demonstrate that IL-4 or OSM stimulates endothelial cells to synthesize more P-selectin over prolonged periods. The increased expression of P-selectin may facilitate the emigration of leukocytes into sites of chronic or allergic inflammation.
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PMID:Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells. 869 Nov 52


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