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 evolution of acute inflammation from initiation through resolution is associated with the changing character of the infiltrating leukocytes. Recruitment of these leukocytes is dependent upon the generation of chemotactic factors that have either global or specific activity for a particular leukocyte. In this manuscript we present data demonstrating that human neutrophils can express mRNA for neutrophil chemotactic factor/interleukin 8 (IL-8), but fail to express mRNA for monocyte chemotactic protein (MCP-1). The expression of IL-8 was observed upon adherence or in response to stimulation with lipopolysaccharide. Maximal IL-8 antigenic production was noted at 24 hrs. These studies demonstrate a disparate expression of chemotactic cytokines by neutrophils.
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PMID:Human neutrophils exhibit disparate chemotactic factor gene expression. 170 91

Intravenous injections of lipopolysaccharide (LPS, 20 micrograms/kg) and of a factor originating from LPS-stimulated macrophage monolayers (Neutrophil Recruitment Inhibitory Factor, NRIF) inhibited neutrophil migration into peritoneal cavities induced by carrageenin in rats for up to 24 h. Mononuclear cell migration induced by thioglycollate was also inhibited by the same treatment with LPS but was not affected by NRIF. We conclude that NRIF specifically blocks neutrophil migration and we suggest that NRIF released into the circulation may constitute an important determinant of septicemia.
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PMID:Macrophages stimulated with lipopolysaccharide release a selective neutrophil recruitment inhibitory factor: an in vivo demonstration. 262 Jan 85

Endotoxin (lipopolysaccharide, LPS) is known to induce inflammatory responses, such as monocyte/macrophage adherence, migration, and accumulation. Recruitment and accumulation of macrophages during infection and inflammation are regulated by integrin-mediated cell-extracellular matrix interactions. In the present report, we studied the effects of LPS on the expression of VLA-5 (alpha 5 beta 1), VLA-3 (alpha 3 beta 1), and VLA-2 (alpha 2 beta 1) integrins and fibronectin (FN) by human alveolar macrophages in an attempt to understand the mechanism by which LPS regulates macrophage adhesion to matrix proteins. Bronchoalveolar lavage macrophages were treated with varying concentrations of Escherichia coli LPS for different times and evaluated for expression of the integrins and FN by immunofluorescence, immunoelectron microscopy, autoradiography, and radioimmunoassay. Immunofluorescent and immunoelectron microscopic observations showed that VLA integrins were constitutively expressed on the cell surface and concentrated on the microvilli and pseudopodia of the macrophages. The effects of LPS on expression of the integrins were dose and time related. VLA-5 expression was increased after 30 min of stimulation by LPS, suggesting that LPS may induce rapid secretion of the integrin. However, incubations with LPS longer than 30 min decreased VLA-5 expression in a dose-dependent pattern. LPS also caused dose-related decreases in the expression of VLA-3 and VLA-2 integrins and increases of intracellular FN 24 h after stimulation. The results suggest that a prolonged exposure to LPS may impede VLA integrin-mediated migration and result in local accumulation of macrophages in the lung.
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PMID:Effects of endotoxin on expression of VLA integrins by human bronchoalveolar lavage macrophages. 772 20

Inhalation of lipopolysaccharide (LPS) by humans rapidly recruits neutrophils to alveolar structures. Recruitment of neutrophils may be mediated in part by intrapulmonary release of cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-8, although the kinetics of cytokine accumulation and neutrophil recruitment to the lungs after LPS inhalation have not been determined. Release of some cytokines in response to LPS is reported to be decreased in smokers' alveolar macrophages compared with nonsmokers', suggesting responses to LPS may differ in smokers (S) and nonsmokers (NS). To assess the kinetics of early cytokine accumulation after LPS inhalation and to compare inflammation induced in LPS-exposed S and NS, we performed bronchoalveolar lavage (BAL) in 28 subjects (14 NS and 14 S) at 90 or 240 minutes after inhalation of aerosolized LPS (30 microg). BAL performed at 90 and 240 minutes after LPS inhalation recovered increased numbers of neutrophils and lymphocytes in both NS and S compared with an unexposed control group (10 NS, 10 S), with greater recovery of neutrophils in S than NS (p < 0.001). BAL fluid supernate concentrations of IL-8, IL-1beta, and tumor necrosis factor-alpha at 90 minutes were increased in S and NS compared with an unexposed control group. IL-8 and tumor necrosis factor-alpha concentrations were similar in S and NS; however, IL-1beta concentrations were greater in S (p < 0.005). BAL fluid concentrations of IL-1beta and IL-8 at 90 minutes correlated with absolute neutrophil recovery in S and NS. These findings suggest that the rapid accumulation of cytokines, particularly IL-1beta and IL-8, contributes to lung neutrophil recruitment after LPS inhalation. In addition, parameters of pulmonary inflammation present in S after LPS inhalation are similar to or increased compared with those present in NS.
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PMID:Rapid lung cytokine accumulation and neutrophil recruitment after lipopolysaccharide inhalation by cigarette smokers and nonsmokers. 901 86

The pulmonary host response to infection and inflammation appears, at least in part, to be compartmentalized from the systemic host response. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in lung inflammation and injury, but its site(s) of action has not been clearly defined. To investigate this, transgenic mice (surfactant apoprotein C promotor/soluble TNF receptor type II-Fc fusion protein ([SPCTNFRIIFc] mice) were generated in which TNF-alpha was selectively antagonized in the distal lung through tissue-specific expression of sTNFRIIFc, a soluble TNF inhibitor. The lung inflammatory response in these mice to pulmonary challenge with Micropolyspora faeni antigen or lipopolysaccharide (LPS) was compared with the response of wild-type mice, wild-type mice treated with recombinant sTNFRIIFc intravenously, and type I TNF-receptor knockout mice. Recruitment of polymorphonuclear leukocytes (PMN) to the lung after challenge with M. faeni antigen was essentially abolished in the TNFRI knockout mice and markedly reduced in the SPCTNFRIIFc mice. Wild-type mice given sTNFRIIFc intravenously in amounts resulting in lung concentrations similar to those in SPCTNFRIIFc mice also showed significantly reduced lung PMN recruitment, whereas those given doses that achieved such concentrations in the blood but low levels in the lung did not. In contrast, PMN recruitment to the lung following aerosol challenge with LPS was reduced significantly in the TNFRI knockout mice and in mice given high-dose sTNFRIIFc intravenously, but was not reduced significantly in SPCTNFRIIFc mice. Thus, inhibition of PMN recruitment in response to M. faeni antigen correlated largely with the extent of intrapulmonary inhibition of TNF-alpha, whereas the response to LPS correlated best with the extent of extrapulmonary inhibition of TNF-alpha. These studies indicate that TNF-alpha may act at different loci to mediate lung inflammation, with the site of action depending in part on the nature of the inflammatory stimulus, and that SPCTNFRIIFc mice provide a tool by which the locus of TNF action can be addressed.
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PMID:The locus of tumor necrosis factor-alpha action in lung inflammation. 984 22

Tissue eosinophilia is a hallmark of allergic and parasitic diseases. Priming mechanisms may play an important role in mediating the process of eosinophil accumulation in these conditions. We have previously shown that blockade of tumour necrosis factor alpha (TNFalpha) inhibited the capacity of lipopolysaccharide to prime skin sites for chemoattractant-induced eosinophil recruitment. The present study was carried out to investigate the capacity of TNFalpha to prime an inflammatory site for enhanced eosinophil accumulation. Initial experiments investigated the capacity of TNFalpha itself to induce eosinophil accumulation. Intradermal injection of murine TNFalpha (10-300 ng per site) in the guinea-pig induced significant accumulation of 111In-eosinophils. Kinetic studies showed the response to be delayed in onset and inhibited by cycloheximide, consistent with a dependency on protein synthesis. Trafficking of 111In-eosinophils to sites treated for 2 h with TNFalpha (10-100 ng per site) was inhibited by monoclonal antibodies (mAbs) against beta2 or alpha4 integrins. Intradermal injection of a low dose (3 ng) of TNFalpha (which by itself had no significant effect on eosinophil trafficking) prior to chemoattractants or antigen in sensitized skin sites, induced significant priming of eosinophil accumulation. Recruitment of both 111In-eosinophils and endogenous eosinophils was enhanced. Trafficking to TNFalpha-primed responses was dependent on protein synthesis and beta2 integrins. In contrast, the alpha4 integrin mAb failed to inhibit the TNFalpha primed response. Thus, TNFalpha can induce and also prime eosinophil recruitment in guinea-pig skin. Our results provide further evidence that this cytokine may be an important mediator of allergic- or parasite-induced eosinophilic inflammation.
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PMID:Priming and induction of eosinophil trafficking in guinea-pig cutaneous inflammation by tumour necrosis factor alpha. 986 51

Habitual use of smokeless tobacco leads to accumulation of inflammatory leukocytes at the site of placement, which may contribute to tissue damage. Recruitment of leukocytes is facilitated by the endothelial lining of blood vessels, which can be activated to express adhesion molecules and to produce chemoattractants. The ability of aqueous extracts of chewing tobacco, dry snuff, and moist snuff to stimulate such changes was investigated using cultured human umbilical vein endothelial cells (HUVEC). All three extracts caused HUVEC to express the adhesion molecule E-selectin and to produce the chemokines interleukin-8 and monocyte chemoattractant protein-1. Neutrophils migrated avidly across HUVEC monolayers that had been previously exposed to the extracts, whereas migration across unstimulated monolayers was negligible. The smokeless tobacco extracts contained relatively high concentrations of bacterial lipopolysaccharide (LPS). Although LPS appeared to be the major stimulatory component in extracts of chewing tobacco, it accounted for only part of the activity found in extracts of moist and dry snuffs. These observations suggest that smokeless tobacco may induce inflammatory changes in vivo by activating endothelium in a manner that promotes recruitment of leukocytes.
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PMID:Extracts of smokeless tobacco induce pro-inflammatory changes in cultured human vascular endothelial cells. 1070 6

Recruitment of neutrophils to lung tissue and airspaces is a hallmark of inflammatory events following inhalation of endotoxins. We studied the role of different lymphocyte subsets in this inflammation, which is assumed to primarily involve the innate immune system. Inhalation of aerosolized Escherichia coli lipopolysaccharide (LPS) in mice induced a dose-dependent increase in neutrophils in bronchoalveolar lavage fluid, reaching a maximum after 12 h at a low dose and after 24 h at a high dose. Profiles of gene expression in lung tissue indicated an early (2 h) and transient onset of proinflammatory cytokines and chemokines by a low dose of LPS, while a high dose caused more delayed and sustained (6 to 12 h) activation. Gamma interferon, interleukin-2 (IL-2), RANTES, and the alpha chain of the IL-2 receptor were not expressed at a low dose, whereas a high dose of LPS induced a strong expression of these genes, indicating a dose-dependent activation of T cells. A similar pattern was observed for IL-17, supporting a contribution of T cells to the neutrophilic inflammation only at high-dose exposure to LPS. The involvement of lymphocytes in the inflammatory response was further studied using mice with functional deficiencies in defined lymphocyte subsets. Both gammadelta T-cell- and B-cell-deficient mice displayed a response similar to that of the corresponding wild-type strains. Selective depletion of NK cells by in vivo administration of the pk136 antibody did not significantly affect the recruitment of neutrophils into airspaces. Thus, neither NK cells, B cells, nor gammadelta T cells appeared to participate in the host response, suggesting that among the lymphocyte subsets, alphabeta T cells are exclusively involved in endotoxin-induced airway inflammation.
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PMID:Dose-dependent activation of lymphocytes in endotoxin-induced airway inflammation. 1108 20

Interactive contact between B lymphocytes and T cells is necessary for their expansion during an immune response. It has been shown that B lymphocytes receive signals from T cells, such as IL-4 and cross-linking of CD40, which are crucial for their differentiation. We previously found that these factors induce formation of microvilli on B cells and that this was correlated with increased homotypic adhesion of B lymphocytes. In this study we have investigated if IL-4 induce segregation of proteins to microvilli and lipid rafts. Using immuno-electron microscopy we analyzed cell-surface distribution of molecules involved in B-T cell co-activation. Recruitment to detergent-resistant membrane fractions was analyzed using sucrose gradient centrifugation. We found that microvilli were enriched in ICAM-1 and MHC class II molecules. In contrast, LFA-1 and CD40 were more abundant on the smooth cell surfaces, while B7-2 (CD86) was randomly distributed. We also discovered that depletion of cholesterol, using beta-methyl-cyclodextrin, lowered the number of microvilli, indicating that intact lipid rafts are required for their expression. Moreover, activation of B lymphocytes by lipopolysaccharide (LPS) induced increased expression of GM(1), a marker for lipid rafts. However, although both surface and total levels of GM(1) were similar in B lymphocytes stimulated with either LPS or LPS plus IL-4, GM(1) was mainly expressed on microvilli in LPS plus IL-4-stimulated cells. Taken together, our results indicate that microvilli represent distinct inducible membrane domains that can regulate direct cell-cell interactions via grouping and three-dimensional presentation of cell-surface receptors.
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PMID:Microvilli structures on B lymphocytes: inducible functional domains? 1473 21

Transcriptional activators interact with diverse proteins and recruit transcriptional machinery to the activated promoter. Recruitment of the Mediator complex by transcriptional activators is usually the key step in transcriptional activation. However, it is unclear how Mediator recognizes different types of activator proteins. To systematically identify the subunits responsible for the signal- and activator-specific functions of Mediator in Drosophila melanogaster, each Mediator subunit was depleted by RNA interference, and its effect on transcriptional activation of endogenous as well as synthetic promoters was examined. The depletion of some Mediator gene products caused general transcriptional defects, whereas depletion of others caused defects specifically related to activation. In particular, MED16 and MED23 were required for lipopolysaccharide- and heat-shock-specific gene expression, respectively, and their activator-specific functions appeared to result from interaction with specific activators. The corequirement of MED16 for other forms of differentiation-inducing factor-induced transcription was confirmed by microarray analysis of differentiation-inducing factor (DIF)- and MED16-depleted cells individually. These results suggest that distinct Mediator subunits interact with specific activators to coordinate and transfer activator-specific signals to the transcriptional machinery.
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PMID:MED16 and MED23 of Mediator are coactivators of lipopolysaccharide- and heat-shock-induced transcriptional activators. 1529 16


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