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)

PECAM-1 expression was investigated in primary cultures of human brain microvessel endothelial cells (HBMEC). HBMEC constitutively express PECAM-1 along their apical cell surface, advancing processes and on the basal surface at points of contact with the extracellular matrix. Surface expression is not altered by cytokine or lipopolysaccharide treatment. This distribution may mediate cell-cell contract and migration during angiogenesis and HBMEC-leukocyte interactions in CNS inflammation.
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PMID:Platelet/endothelial cell adhesion molecule-1 (PECAM-1) expression by human brain microvessel endothelial cells in primary culture. 888 74

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

To help assess the immunological functions of the liver peritoneum, expression and 3D-microlocalization of adhesion molecules were studied by immuno-SEM and -TEM. The peritoneal tissues of the liver obtained from lipopolysaccharide (LPS, 1.5 microg/g BW for 24 hr)-stimulated (n = 18 including nine controls) and non-stimulated mice (n = 6 including three controls) were analyzed by immunolabeling with 15 nm gold particle single-labeling analysis of ICAM-1, ICAM-2, VCAM-1, MAdCAM-1, PECAM-1, ELAM-1, and CD105 expression. In addition, 10 and 20 nm gold particle double-labeling analysis of ICAM-1 and VCAM-1 was carried out with conventional TEM and BSE (backscatter electron) imaging. Gold particles detected in the peritoneal mesothelial cells were quantified using a computer analyzer, LUZEX III. Only ICAM-1 in non-stimulated mice and both ICAM-1 and VCAM-1 in LPS-stimulated mice were expressed on the mesothelium, but no other adhesion molecules were detected in either condition. Expression of ICAM-1 was consistently about four times greater than that of VCAM-1. Each adhesion molecule was restricted to the microvilli. ICAM-1 was expressed on all microvilli and tended to form clusters of three or four molecules. On the other hand, about 24% of the microvilli expressed VCAM-1 and less clustering was seen. Double-labeling techniques disclosed that VCAM-1 and ICAM-1 were rarely closely associated, usually spaced by about 40 nm. These results suggest that microvilli of the mesothelial cell play a significant role in leukocyte migration in the peritoneal cavity, by providing the important substrates for adhesion, ICAM-1 and VCAM-1.
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PMID:Expression of adhesion molecules relevant to leukocyte migration on the microvilli of liver peritoneal mesothelial cells. 1060 47

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is an immunoglobulin-immunoreceptor tyrosine-based inhibitory motif (Ig-ITIM) superfamily member that recruits and activates protein-tyrosine phosphatases, SHP-1 and SHP-2, through its intrinsic ITIMs. PECAM-1-deficient (PECAM-1(-/-) ) mice exhibit a hyperresponsive B-cell phenotype, increased numbers of B-1 cells, reduced B-2 cells, and develop autoantibodies. In the periphery, there are reduced mature recirculating B-2 cells and increased B-1a cells within the peritoneal cavity. In addition, PECAM-1(-/-) B cells display hyperproliferative responses to lipopolysaccharide and anti-IgM stimulation and showed enhanced kinetics in their intracellular Ca(++) response following IgM cross-linking. PECAM-1(-/-) mice showed increased serum levels of IgM with elevated IgG isotypes and IgA antidinitrophenol antibody in response to the T-independent antigen, dinitrophenol-Ficoll. Finally, PECAM-1(-/-) mice developed antinuclear antibodies and lupuslike autoimmune disease with age.
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PMID:Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and autoimmune disease. 1207 26

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

In vitro and in vivo evidence supports a functional role for the integrin alpha6beta1 in neutrophil migration through the perivascular basement membrane, a response that in vivo appears to be associated with platelet/endothelial cell adhesion molecule-1 (PECAM-1)-mediated up-regulation of alpha6beta1 on the cell surface of transmigrating leukocytes. As the involvement of PECAM-1 in leukocyte migration is cytokine-specific, the aim of the present study was to investigate whether alpha6beta1 exhibited a similar profile of stimulus specificity in this context. The cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) were used to elicit neutrophil migration in two murine models of inflammation, migration through cremasteric venules, as observed by intravital microscopy, and migration into the peritoneal cavity. The role of alpha6beta1 was investigated using an alpha6 integrin-blocking monoclonal antibody GoH3. In both models, GoH3 significantly inhibited neutrophil transmigration induced by IL-1beta but not TNF-alpha. This cytokine-specific role of alpha6 integrin was associated with enhanced cell-surface expression of alpha6beta1 on transmigrated neutrophils (as compared with blood cells) in response to IL-1beta but not TNF-alpha. Using lipopolysaccharide as an inflammatory stimulus in the cremaster muscle model, the study also provides evidence for the involvement of alpha6 integrin in leukocyte transmigration as mediated by endogenously generated IL-1beta. Collectively, the findings demonstrate that alpha6beta1 blockade inhibits neutrophil migration induced by exogenous and endogenous IL-1beta but not TNF-alpha, observations that are associated with increased expression of the integrin on transmigrated leukocytes.
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PMID:Blockade of alpha6 integrin inhibits IL-1beta- but not TNF-alpha-induced neutrophil transmigration in vivo. 1553 57

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), an adhesion molecule expressed on hematopoietic and endothelial cells, mediates apoptosis, cell proliferation, and migration and maintains endothelial integrity in addition to its roles as a modulator of lymphocyte and platelet signaling and facilitator of neutrophil transmigration. Recent data suggest that CD31 functions as a scaffolding protein to regulate phosphorylation of the signal transducers and activators of transcription (STAT) family of signaling molecules, particularly STAT3 and STAT5. STAT3 regulates the acute phase response to innate immune stimuli such as lipopolysaccharide (LPS) and promotes recovery from LPS-induced septic shock. Here we demonstrate that CD31-deficient mice have reduced survival during endotoxic LPS-induced shock. As compared to wild-type controls, CD31-deficient mice showed enhanced vascular permeability; increased apoptotic cell death in liver, kidney, and spleen; and elevated levels of serum tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFNgamma), MCP-1, MCP-5, sTNRF, and IL-6. In response to LPS in vivo and in vitro, splenocytes and endothelial cells from knockout mice had reduced levels of phosphorylated STAT3. These results suggest that CD31 is necessary for maintenance of endothelial integrity and prevention of apoptosis during septic shock and for STAT3-mediated acute phase responses that promote survival during septic shock.
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PMID:Enhanced susceptibility to endotoxic shock and impaired STAT3 signaling in CD31-deficient mice. 1563 11

Human pulmonary microvascular endothelial cell (HPMVEC) injury is central to the pathophysiology of human lung injury. However, septic HPMVEC barrier dysfunction and the contribution of neutrophils have not been directly addressed in vitro. Instead, human EC responses are often extrapolated from studies of human umbilical vein EC (HUVEC). We hypothesized that HUVEC was not a good model for investigating HPMVEC barrier function under septic conditions. HPMVEC was isolated from lung tissue resected from lung cancer patients using magnetic bead-bound anti-PECAM-1 antibody. In confluent monolayers in 3-mum cell-culture inserts, we assessed trans-EC Evans-Blue (EB)-conjugated albumin leak under basal, unstimulated conditions and following stimulation with either lipopolysaccharide or a mixture of equal concentrations of TNF-alpha, IL-1beta and IFN-gamma (cytomix). Basal EB-albumin leak was significantly lower across HPMVEC than HUVEC (0.64 +/- 0.06% vs. 1.13 +/- 0.10%, respectively, P < 0.001). Lipopolysaccharide and cytomix increased leak across both HPMVEC and HUVEC in a dose-dependent manner, with a similar increase relative to basal leak in both cell types. The presence of neutrophils markedly and dose-dependently enhanced cytomix-induced EB-albumin leak across HPMVEC (P < 0.01), but had no effect on EB-albumin leak across HUVEC. Both cytomix and lipopolysaccharide-induced albumin leak was not associated with a loss of cell viability. In conclusion, HPMVEC barrier dysfunction under septic conditions is dramatically enhanced by neutrophil presence, and HUVEC is not a suitable model for studying HPMVEC septic barrier responses. The direct study of HPMVEC septic responses will lead to a better understanding of human lung injury.
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PMID:Albumin leak across human pulmonary microvascular vs. umbilical vein endothelial cells under septic conditions. 1637 51

A new compliant scaffold suitable for small-diameter vascular grafts has been developed that promotes strong attachment of endothelial cells. Composite scaffolds were produced by wet spinning polycaprolactone (PCL) fibres which form the luminal surface, then electrospinning porous polyurethane (PU) onto the back of the PCL fibres to form the vessel wall substitute. Human endothelial cells demonstrated strong attachment to the composite PCL-PU scaffold, and proliferated to form a monolayer with strong PECAM-1 expression and cobblestone morphology. Attached cells demonstrated abundant release of von Willebrand factor, nitric oxide and ICAM-1 under physiological stimuli, and exhibited an immune response to lipopolysaccharide. The composite scaffold may also deliver bioactive molecules. Active trypsin, used as a test molecule, had a defined 48 h pattern of release from luminal PCL fibres. These data confirm the potential of this novel composite scaffold in vascular tissue engineering.
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PMID:PCL-PU composite vascular scaffold production for vascular tissue engineering: attachment, proliferation and bioactivity of human vascular endothelial cells. 1653 Aug 24

The establishment of a functional vasculature is as yet an unrealized milestone in bone reconstruction therapy. For this study, fiber-mesh scaffolds obtained from a blend of starch and poly(caprolactone) (SPCL), that have previously been shown to be an excellent material for the proliferation and differentiation of bone marrow cells and thereby represent great potential as constructs for bone regeneration, were examined for endothelial cell (EC) compatibility. To be successfully applied in vivo, this tissue engineered construct should also be able to support the growth of ECs in order to facilitate vascularization and therefore assure the viability of the construct upon implantation. The main goal of this study was to examine the interactions between ECs and SPCL fiber meshes. Primary cultures of HUVEC cells were selected as a model of macrovascular cells and the cell line HPMEC-ST1.6R as a model for microvascular ECs. Both macro- and microvascular ECs adhered to SPCL fiber-mesh scaffolds and grew to cover much of the available surface area of the scaffold. In addition, ECs growing on the SPCL fibers exhibited a typical morphology, maintained important functional properties, such as the expression of the intercellular junction proteins, PECAM-1 and VE-cadherin, the expression of the most typical endothelial marker vWF and sensitivity to pro-inflammatory stimuli, as shown by induction of the expression of cell adhesion molecules (CAMs) by lipopolysaccharide (LPS). These data indicate that ECs growing on SPCL fiber-mesh scaffolds maintain a normal expression of EC-specific genes/proteins, indicating a cell compatibility and potential suitability of these scaffolds for the vascularization process in bone tissue engineering in vivo.
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PMID:Response of micro- and macrovascular endothelial cells to starch-based fiber meshes for bone tissue engineering. 1694 11


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