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)

By using flow cytometric analysis of cells in whole blood expressing high levels of CD14, we found a subpopulation of monocytes (8% of total) with higher scatter parameters, high capacity to produce reactive oxygen species (ROS), stronger expression of Lewis-X (CD15), sialyl-Lewis-X, CD11b and CD18 antigens, as well as an increased polymerized actin content. The size of this subpopulation increased after stimulation with lipopolysaccharide at the expense of the remaining monocytes, suggesting that its features were inducible. The membrane increase in Lewis-X and sialyl-Lewis-X expression observed during this conversion was largely due to the translocation of these carbohydrate structures from intracellular pools. Moreover, this subpopulation behaved as a primed monocyte subpopulation producing large amounts of H2O2 in response to N-formyl-methionyl-leucyl-phenylalanine. Increased H2O2 production was inhibited not only by anti-CD14 but also by anti-CD15 and anti-sialyl-Lewis-X monoclonal antibodies when added before lipopolysaccharide. These results show that lipopolysaccharide priming is regulated, at least in part, by Lewis-X and sialyl-Lewis-X structures expressed on the monocyte membrane. All together, this highly reactive and inducible subpopulation of monocytes, which share phenotypic and functional characteristics with neutrophils, might play an important role in host defenses and inflammatory responses.
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PMID:Heterogeneity in Lewis-X and sialyl-Lewis-X antigen expression on monocytes in whole blood: relation to stimulus-induced oxidative burst. 954 69

To identify the role in periodontal inflammatory diseases of human gingival fibroblasts (HGF), the major constituents of gingival tissue, the expression of CD14, a possible lipopolysaccharide (LPS) receptor, and the release of soluble CD14 (sCD14) by HGF were examined. Among the HGF samples from the nine donors tested, more than 50% of the HGF from five donors expressed CD14 but less than 20% of HGF from the other four donors did so, as determined by flow cytometric analysis. The CD14 expression on the cell surface was correlated with the expression of CD14 mRNA. The HGF and skin and lung fibroblasts tested expressed no CD18, which indicates that fibroblasts do not possess other LPS receptors, such as CD11b/CD18 and CD11c/CD18. The CD14 expression by the HGF was decreased after subculturing and was highest at the confluent stage of culture. The treatment of high-CD14-expressing (CD14(high)) HGF with phosphatidylinositol-phospholipase C reduced CD14 expression; this result and the increase in a 55-kDa CD14 indicate that the membrane CD14 (mCD14) on the HGF may be a 55-kDa glycosylphosphatidylinositol-anchored protein. CD14(high) HGF spontaneously released 48- and 57-kDa sCD14. The total release of sCD14 by the HGF was augmented by gamma interferon and Escherichia coli LPS in accordance with the increased expression of mCD14. The CD14(high) HGF secreted interleukin-8 in response to LPS, and the secretion was completely inhibited by anti-CD14 antibody. These results suggest that (i) HGF consist of populations that are heterogeneous on the basis of different levels of expression of CD14 and (ii) CD14(high) HGF secrete inflammatory cytokines in response to LPS via CD14.
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PMID:Heterogeneous expression and release of CD14 by human gingival fibroblasts: characterization and CD14-mediated interleukin-8 secretion in response to lipopolysaccharide. 963 64

We report a novel technique that may allow site-specific gene delivery into inflamed tissues. Bone marrow cells from DBA/2 mice were incubated for 7 days in L-929 cell-conditioned medium containing elements that favor the development of mononuclear cells, such as colony-stimulating factors. Flow cytometric analysis revealed that 99.1 +/- 0.9% of the subcloned cells were positive for CD11b and CD18, both of which are ligands of the intercellular adhesion molecule 1 (ICAM-1). These vehicle cells were labeled with a fluorescent lipophilic probe and returned intravenously to the DBA/2 mice. The mice then received, for 1 week, intraperitoneal injections of either lipopolysaccharide (LPS) to enhance ICAM-1 expression in the glomerulus, or saline as a control. In the LPS-treated mice, labeled vehicle cells were detected within the glomerulus cross-section (gcs) 24 hr after the first injection (0.73 +/- 0.10/gcs). The number of labeled vehicle cells within the glomerulus gradually increased for 1 week (1.47 +/- 0.19/gcs) and decreased after discontinuation of the LPS injections. However, in the saline-treated control group, only a negligible number of vehicle cells could be detected in the glomerulus (0.05 +/- 0.03/gcs). A second administration of LPS 4 weeks after injection of the vehicle cells was also able to promote accumulation in the glomerulus. Furthermore, immunohistochemical analysis revealed that the kinetics of the vehicle cell recruitment into the glomerulus corresponded to the level of ICAM-1 expression. On the assumption that the LPS-induced ICAM-1 expression may regulate the site and timing of the delivery of vehicle cells into the glomerulus, vehicle cells were transduced with human glucocerebrosidase (GC) gene, using an adenovirus vector, and reintroduced into the mice. The basal expression of GC gene in the isolated glomeruli of vehicle cell-treated mice rose by 1.7-fold compared with endogenous activity, whereas the GC activity was enhanced 3.2-fold by LPS treatment. Polymerase chain reaction designed to detect human GC-specific sequence revealed that isolated glomeruli of vehicle cell-treated mice contained exclusively the vehicle cell-oriented GC. This indicates that vehicle cells can be used to carry a certain gene to a specific inflamed site. Injection of vehicle cells, with or without LPS, had small effect on urinary protein excretion or serum creatinine levels. These findings suggest that our novel method allows site-specific gene delivery into inflamed glomeruli through interaction of adhesion molecules.
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PMID:Inflamed site-specific gene delivery using bone marrow-derived CD11b+CD18+ vehicle cells in mice. 972 Oct 83

It was recently proposed that nitric oxide (NO) inhalation interferes with polymorphonuclear neutrophil (PMN) activation status during acute pulmonary inflammation, although variable results have been observed considering timing of NO administration, species, and model differences. After intratracheal administration of lipopolysaccharide (LPS) in rats, we characterized pulmonary inflammatory reaction (lung wet, dry, and wet to dry weights) and, using flow cytometry, the activation status (H2O2 production and beta2 integrin CD11b/CD18 expression) of PMN obtained from blood and from bronchoalveolar lavage (BAL). Eight hours after LPS injection, rats received for an additional 10 h, at a same Fio2 (85%), either 15 parts per million NO or the same gas flow of nitrogen. We found that 18 h after LPS, lung wet, dry, and wet-to-dry weights, H2O2 production, and CD11b/CD18 expression were increased. PMN obtained from BAL were highly activated as evidenced by an already maximal expression of the beta2 integrin CD11b/CD18, whereas the high H2O2 production at basal state could be further enhanced after ex vivo stimulation. Blood PMN were not different from control cells at basal state; however, their increased capacity to be stimulated ex vivo suggested an in vivo priming effect of intratracheal LPS. In conclusion, inhaled NO, given with a high FiO2, in the presence of this established endotoxinic lung injury did not reverse the markers of PMN activation studied nor lung edema formation in this rat model.
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PMID:Alveolar neutrophil oxidative burst and beta2 integrin expression in experimental acute pulmonary inflammation are not modified by inhaled nitric oxide. 972 80

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

Coagulation is intimately involved in the pathology of inflammation. The leukocyte beta2-integrins have several functions, including serving as receptors for coagulation factor X and fibrinogen. Tissue factor (TF) is a receptor for factor VII and a very potent trigger of coagulation. The intention of this study was to examine a possible coexpression of beta2-integrins (CD11b/CD18 and CD11c/CD18) and the procoagulant TF in alveolar macrophages (AM) and blood monocytes, i.e. cells of the same differentiation lineage. The expression of beta2-integrins in human AM isolated by bronchoalveolar lavage and in blood monocytes was analysed by flow cytometry, whereas TF activity was analysed in a one-stage clotting assay. In monocytes, TF activity, CD11b and CD11c expression were highly inducible by lipopolysaccharide (LPS), with a 13-, 19- and four-fold increase, respectively. In AM, TF and beta2-integrins were all constitutively expressed, but the expression could not be further enhanced by LPS stimulation. CD11b and CD11c expression varied inversely with the cell size of AM, in contrast to TF activity which is known to be proportional to AM cell size. In vitro expression of beta2-integrins and tissue factor in lipopolysaccharide-stimulated blood monocytes seems to be intimately coregulated, whereas the expression of these receptors in alveolar macrophages seems to be unresponsive to lipopolysaccharide. These results indicate that blood monocytes and alveolar macrophages have different roles and use different mechanisms in cell-induced fibrin formation.
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PMID:Expression of leukocyte integrins and tissue factor in mononuclear phagocytes. 976 87

Immune mechanisms, including production of pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF), play an important role in early atherogenesis. The study of the mechanisms responsible for the increased cytokine production capacity of hypercholesterolemic hosts is therefore crucial for finding new strategies aimed to stop the development of atherosclerosis. We assessed the lipopolysaccharide (LPS)-induced cytokine production of macrophages from low-density lipoproteins (LDL)-receptor knock-out (LDLR-/-) mice, which have a seven- to ninefold higher plasma LDL concentration. Macrophages of LDLR-/- mice produced approximately twofold more IL-1alpha and IL-1beta in response to LPS when compared with macrophages of control mice (LDLR+/+). TNF-alpha synthesis was only slightly increased. Removal of CD14 by phospholipase C treatment of cells decreased cytokine production by 50% (IL-1) to 80% (TNF), but the differences between LDLR-/- and LDLR+/+ remained the same. In contrast, treatment of cells with anti-CD11c monoclonal antibody inhibited the IL-1alpha and IL-1beta production in LDLR-/- mice towards normal values, while no effect could be seen on TNF. In conclusion, LDLR-/- macrophages stimulated with LPS synthesize more IL-1alpha and IL-1beta than controls and this phenomenon is mediated by the CD11c/CD18 receptor.
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PMID:Increased interleukin-1alpha and interleukin-1beta production by macrophages of low-density lipoprotein receptor knock-out mice stimulated with lipopolysaccharide is CD11c/CD18-receptor mediated. 982 12

Bacterial lipopolysaccharide (LPS) is a potent activator of cells of the macrophage/monocyte lineage. Two mature macrophage cell lines, P388D1 and RAW264.7, exhibit very different biological responses to LPS. Although RAW264.7 cells release arachidonic acid from phospholipid in response to LPS stimulation, P388D1 cells do not respond in this manner. However, LPS primes P388D1 cells to release arachidonic acid in response to other stimuli. The goal of this work is to contrast the biochemical events that occur in LPS-treated P388D1 and RAW264.7 macrophages. Enzyme assays indicate that LPS treatment induces the activation of cytosolic PLA2 in RAW264.7, but not in P388D1 cells. Phorbol ester (PMA), a receptor-independent stimulus, also fails to induce arachidonic acid release from P388D1 cells, suggesting that these cells may have a defect in the signal transduction machinery that is common to LPS and PMA. This hypothesis is supported by the observation that the expression of the LPS receptors CD14 and CD11b/CD18 is similar on P388D1 and RAW264.7 cells. Western blot analyses indicate that the erk kinases are activated upon LPS treatment of RAW264.7 but not P388D1 cells. LPS-induced arachidonic acid release is reduced in cells treated with the MEK inhibitor PD98059, suggesting that activated erk kinases mediate the phosphorylation and activation of cPLA2 in this system. Interestingly, the p42 isoform of erk (erk2) appears to be activated in resting P388D1 cells. This observation indicates that the MAP kinase cascade may be constitutively activated in P388D1 cells which may in turn limit their ability to respond to LPS. Together, these data provide evidence that mature macrophages from different sources can exhibit variable responses to LPS and highlight the danger of making generalizations regarding the effects of LPS on macrophages.
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PMID:Mature macrophage cell lines exhibit variable responses to LPS. 988 93

PU.1 is a transcription factor found in macrophages, B cells, neutrophils, and hemopoietic stem cells. In macrophages PU.1 regulates a number of genes, including c-fms, CD11b, CD18, and FcgammaR1b. Previously, in primary macrophages PU.1 binding to the sequence GAGGAA was found to be induced by treatment with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Here we investigated the role of protein kinase C (pKC) in the induction of PU.1 binding in macrophages. We report that pharmacological activation of pKC increases PU.1 binding, while inactivation of pKC inhibits the increases in PU.1 binding by agents which activate pKC in macrophages (LPS and tumor necrosis factor-alpha), but not by an agent which does not activate pKC (IFN-gamma). pKC activation may therefore be one pathway by which PU.1 binding may be increased in primary macrophages.
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PMID:Protein kinase C activation increases binding of transcription factor PU.1 in murine tissue macrophages. 992 Jul 60

Cell adhesion molecules have a key role in the migration of T cells to inflammatory foci. However, the effect of the endothelial-lymphocyte interaction on the activation of the latter cells remains unresolved. We have studied the effect of resting and stimulated endothelial cells (ECs) on the activation of peripheral blood T cells (PBTLs), as assessed by the expression of CD69 and CD25 activation antigens. The incubation of PBTLs with tumor necrosis factor-alpha-activated EC monolayers, either alive or fixed, induced the expression of CD69 but not CD25, preferentially in the CD8(+) CD45RO+ cell subset. Furthermore, it induced the production of cytokines such as IFN-gamma, but not that of interleukin-2 (IL-2) and IL-4. EC treated with other stimuli such as IL-1beta, IFN-gamma, or lipopolysaccharide also showed the same proactivatory effect on T cells. Lymphocyte activation was almost completely inhibited by blocking anti-CD18 and anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibodies (MoAbs), but only slightly affected by MoAbs against CD49d, vascular cell adhesion molecule-1, and anti-IL-15. In addition, the interaction of PBTL with immobilized ICAM-1 induced CD69 expression in the same memory T-cell subset. IL-15 induced T-cell activation with expression of CD69 and CD25, and production of IFN-gamma, and its effect was additive with that triggered by cell adhesion to either EC or immobilized ICAM-1. The transmigration of PBTLs through either confluent EC monolayers or ICAM-1-coated membranes also induced efficiently the expression of CD69. When IL-15 was used as chemoattractant in these assays, a further enhancement in CD69 expression was observed in migrated cells. Together these results indicate that stimulated endothelium may have an important role in T-cell activation, through the lymphocyte function antigen-1/ICAM-1 pathway, and that IL-15 efficiently cooperates in this phenomenon. These observations could account for the abundance of CD69(+) cells in the lymphocytic infiltrates of several chronic inflammatory diseases.
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PMID:Activation of peripheral blood T cells by interaction and migration through endothelium: role of lymphocyte function antigen-1/intercellular adhesion molecule-1 and interleukin-15. 992 Aug 37


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