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

Neisseria gonorrhoeae isolated from patients with disseminated infection (DGI) often resist complement (C')-dependent killing by normal human serum (NHS) and less commonly by convalescent DGI serum. 7 of 10 NHS specimens completely inhibited killing of serum-resistant (ser(r)) gonococci by convalescent or immune DGI serum. Immunoglobulin G (IgG) purified from NHS was shown to be the blocking agent. In addition, IgM (plus C') purified from NHS was shown to be fivefold more effective (wt/wt) in killing serum-sensitive (ser(s)) gonococci than equivalent amounts of IgM tested in the presence of IgG (whole serum). Although inhibition of NHS killing of ser(s) gonococci required a 640% excess of IgG, only a 40% excess was required to block immune serum killing of ser(r) gonococci. F(ab')(2) prepared from IgG also blocked killing of ser(r) gonococci by immune serum indicating antigenic specificity of blocking IgG.IgG immunoconcentrated against outer membrane protein (OMP) derived from ser(r) gonococci showed 40-fold increased blocking activity over normal IgG (wt/wt) and lacked antibody activity directed against gonococcal lipopolysaccharide by ELISA. Using direct immunoabsorption of IgG with purified gonococcal OMP; ser(r)-OMP was found sixfold more effective than ser(s)-OMP in neutralizing the blocking of immune serum killing of ser(r) gonococci, and 10-fold more effective in systems that used excess blocking IgG, NHS, and ser(s) gonococci. Blocking IgG preabsorbed with whole ser(r) gonococci lost 75% of its ability to block immune serum killing compared with no loss in this system using a similar absorption with ser(s) gonococci. IgG purified from NHS contained fivefold higher titers of antibody against ser(r)-OMP than ser(s)-OMP by ELISA.
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PMID:Characterization of serum resistance of Neisseria gonorrhoeae that disseminate. Roles of blocking antibody and gonococcal outer membrane proteins. 680 19

Effective T-cell activation requires antigen/major histocompatibility complex engagement by the T-cell receptor complex in concert with one or more costimulatory molecules. Recent studies have suggested that the B7 molecule, expressed on most antigen presenting cells, functions as a costimulatory molecule through its interaction with CD28 on T cells. Blocking the CD28/B7 interaction with CTLA4Ig inhibits T-cell activation in vitro and induces unresponsiveness. We demonstrate that another molecule(s), termed B7-2, is expressed constitutively on dendritic cells, is differentially regulated on B cells, and costimulates naive T cells responding to alloantigen. B7-2 is up-regulated by lipopolysaccharide in < 6 hr and is maximally expressed on the majority of B cells by 24 hr. In contrast, B7 is detected only on a subset of activated B cells late (48 hr) after stimulation. In addition, Con A directly induces B7-2 but not B7 expression on B cells. Finally, although both anti-B7 monoclonal antibodies and CTLA4Ig blocked T-cell proliferation to antigen-expressing B7 transfectants, only CTLA4Ig had any significant inhibitory effect on T-cell proliferation to antigens expressed on natural antigen presenting cells, such as dendritic cells. Thus, B7 is not the only costimulatory molecule capable of initiating T-cell responses since a second ligand, B7-2, can provide a necessary second signal for T-cell activation.
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PMID:Expression and functional significance of an additional ligand for CTLA-4. 750 92

Human neutrophils are primed in the presence of complexes of lipopolysaccharide (LPS) with its serum binding protein (LBP) in a manner dependent on CD14. Cellular consequences of priming include increased responsiveness, the upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac-1), the increased binding of certain ligands to CD11b/CD18, and the concurrent shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18 and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of bacterial endotoxin on the expression of neutrophil adhesive molecules. We observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface numbers and adhesive function of CD11b/CD18 for latex particles, did not induce aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an extent roughly proportional to the available L-selection. Blocking of LPS/LBP with CD14-specific monoclonal antibodies suppressed L-selectin shedding and preserved formyl peptide-stimulated aggregation. Taken together, the data suggest that inhibition of neutrophil aggregation by LPS/LBP is related to the expression of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during cellular stimulation.
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PMID:Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation. 751 6

Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay. There was no significant difference between acne and non-acne subjects. Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination. P. acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells. Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction. The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane. Incubation of P. acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity. The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity. Heating of the P. acnes supernatant to 65 degrees C also had no effect on the activity. Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that the soluble stimulating factor may be a secreted form of peptidoglycan-polysaccharide.
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PMID:Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne. 754 39

Mice of the C57BL/6 strain were injected intraperitoneally with 10(8) sheep red blood cells (SRBC), then instilled intratracheally with 10(8) SRBC two to three weeks later. After a single intratracheal exposure, a significant cellular infiltrate occurred, composed mostly of macrophages and lymphocytes. Lymphocytes proliferated significantly in response to SRBC antigen in vitro and released interleukin-2 (IL-2). Alveolar macrophages isolated from mice challenged with SRBC released higher levels of IL-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) upon in vitro lipopolysaccharide (LPS) stimulation compared to unprimed, challenged mice or mice receiving intraperitoneal SRBC alone. Lymphocytes from primed mice challenged three times with SRBC proliferated significantly less in response to the antigen than mice receiving one SRBC challenge and released significant levels of interferon gamma (IFN-gamma). Bronchoalveolar macrophages isolated from primed mice given three SRBC challenges released slightly higher levels of TNF-alpha and IL-6 in response to LPS than those from unprimed mice. After the third instillation, levels of hydroxyproline in the lungs increased significantly, indicative of a fibrotic reaction. Neutralization of IL-1 (by anti-mouse type 1 IL-1 receptor) or TNF-alpha resulted in the partial abrogation of the initial neutrophil influx, with some effect on the subsequent lymphocyte and macrophage influx. Blocking IL-1 or IL-2 but not TNF-alpha also resulted in a significant decrease in lung hydroxyproline increase, as well as lung granulomatous response and fibrosis. Overall, these results suggest that lymphoproliferation in the lungs in response to an antigen can result in fibrosis, mediated in part by IL-2 and IL-1.
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PMID:Antigen-induced alveolitis: cytokine production in a mouse model. 760 3

Blocking monoclonal antibodies (mAbs) specific to mouse interleukin-1 receptor antagonist (IL-1ra) were prepared by immunizing Armenian hamsters with recombinant mouse IL-1ra. A sensitive and specific ELISA against mouse IL-1ra was also established. In Propionibacterium acnes-induced liver injury, P. acnes induced transient increase of serum tumor necrosis factor-alpha levels but not those of IL-1ra, IL-1, and IL-6. However, subsequent lipopolysaccharide (LPS) challenge induced the increase of serum levels of all these cytokines and the peak serum IL-1ra level was more than 20 times as high as serum IL-1 levels. Immunohistochemical analysis demonstrated that IL-1ra was predominantly produced by hepatocytes during the course of the priming phase by P. acnes and eliciting phase by LPS challenge. Furthermore, the administration of a mAb to mouse IL-1ra exacerbates the liver injury induced by P. acnes and sublethal dose of LPS, suggesting a protective role of endogenous IL-1ra in this liver injury model.
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PMID:Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice. 761 10

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2-integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L-selectin adhesive epitope.
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PMID:Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation. 790 99

Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to examine the LPS-induced production of tumor necrosis factor alpha and interleukin-6 in PNH patients and healthy volunteers. At low endotoxin concentrations (1 ng/ml), PNH patients displayed a marked defect in the production of both cytokines, whereas at high LPS concentrations (100 ng/ml), cytokine production was similar to that in healthy volunteers. Using flow cytometry, we also studied the expression of the adhesion molecules Mac-1 (CD11b/CD18) and ICAM-1 (CD54) by monocytes and granulocytes after LPS stimulation. Compared with phagocytes from healthy volunteers, CD14-deficient cells showed poor Mac-1 and ICAM-1 upregulation when whole blood was stimulated with LPS (1 ng/ml), whereas their response to higher LPS doses (100 and 1,000 ng/ml) was essentially normal. The importance of the CD14 molecule in the activation of phagocytes by low LPS concentrations was confirmed by the inhibitory effect of an anti-CD14 antibody both in healthy volunteers and in PNH patients. Since these patients produce the soluble form of the CD14 molecule, these data suggest that soluble CD14 could play a role in phagocyte responses to LPS. We conclude that, in whole blood, phagocytes from PNH patients show impaired responsiveness to LPS and this phenomenon is most probably related to their defect in expression of membrane CD14.
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PMID:Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria. 769 46

The dependence of the amount of electrokinetic potential in cells of Escherichia coli and Yersinia pestis, which differ in the rate of reduction of lipopolysaccharide (LPS), on the presence or absence of typical and atypical capsules of Y. pestis, encoded by intact and mutant fra operons, respectively, was studied. The ycaA+ycaF+(caf1 M+caf1+) genotype was shown to be expressed in serological stability of a classical capsular antigen, irrespective of the producer strain, and a decrease in the negative charge of microbial cells compared to their noncapsular variants. Blocking of the synthesis of the product of the ycaA gene of the fra operon resulted in formation of encapsulated bacteria, whose surface electricity and serological characters varied in dependence on the LPS structure. Data obtained support the assumption that a product of the ycA gene stabilizes the conformation of the typical capsule of the plague-causing agent, which was formed from YcaF (Caf1) monomers.
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PMID:[Electrokinetic potential of Yersinia pestis and Escherichia coli cells with an intact or defective ycaA gene (caf1M) of the fra-operon of plague pathogen]. 800 99

Spontaneous and mitogen-stimulated proliferation of spleen lymphocytes was inhibited by coculturing the cells with murine bone marrow derived macrophages (BM-M phi). The inhibitory effect was found to be dependent on the maturation stage of BM-M phi reflected by the appearance of the phenotype BM 8 and on the number of BM-M phi added to the lymphocytes. The spontaneous proliferation was only inhibited by the addition of high numbers of BM-M phi of late maturation stage. The lipopolysaccharide (Lps) induced response was strongly suppressed by increasing proportions of BM-M phi of either cultivation stage. The suppressive effect on the concanavalin A (Con A)-induced proliferative activity increased with the maturation of the macrophages. Inhibition of prostanoid release with indomethacin had no effect. Blocking of nitric oxide synthesis partially reversed the inhibitory effect of macrophages mainly on the Con-A response. Addition of culture supernatant of BM-M phi to the lymphocytes did not mimic the effect of the macrophages themselves. BM-M phi only slightly inhibited the proliferation when lymphocyte-BM-M phi cell-to-cell contact was prevented. These results show that BM-M phi differently influence the spontaneous and mitogen-induced lymphoproliferation and that the inhibitory effect of BM-M phi on the lymphocyte proliferation is only partially mediated by secretory products of macrophages but apparently requires cell-to-cell contact between both cell types.
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PMID:Inhibition of spontaneous and mitogen-induced lymphocyte proliferation by murine bone marrow-derived macrophages: role of prostaglandins, nitric oxides and cell-to-cell contact. 802 37


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