UNIPROT:P43026 - FACTA Search

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

The proliferative response of peripheral blood T cells to the spirochete, Borrelia burgdorferi, can be as pronounced in unexposed normal individuals as it is in Lyme disease patients. This finding was observed using three geographically distinct isolates of B. burgdorferi. The response is not due to a lipopolysaccharide effect of the spirochete, is sensitive to Proteinase K, and requires antigen processing. It does not result from cross-reactivity of memory T cells that may be reactive to another antigen; the proliferative response to B. burgdorferi is equally distributed between naive (CD29-, CD45RO-) and memory (CD29+, CD45RO+) T cells, whereas the tetanus response is confined to the memory subset. In support of this notion, cord blood specimens that contain almost entirely naive T cells, respond as vigorously to B. burgdorferi as T cells from normal adult peripheral blood. A large panel of CD4+ T cell clones has been derived that are specific for B. burgdorferi. The majority of these clones are reactive to B. burgdorferi in the presence only of autologous HLA-DR molecules. Collectively, these data suggest that the T cell response from normal individuals is more likely due to multiple antigenic epitopes within Borrelial proteins than a superantigen response.
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PMID:Prominent T lymphocyte response to Borrelia burgdorferi from peripheral blood of unexposed donors. 790 15

A monoclonal immunoglobulin G1 (IgG1) antibody (mAb), designated mNI-11, was produced by immunizing mice with the lipopolysaccharide (LPS)-stimulated monocyte-like cell line U937. The reactivity of mNI-11 was tested by the indirect immunofluorescence method. The antigen defined by mNI-11 was found to be expressed on U937 cells, LPS-stimulated U937 cells, normal CD14+ cells (monocytes/macrophages), and human umbilical vein endothelial cells (HUVECs). Expression of the antigen defined by mNI-11 on HUVECs slightly increased in response to exposure to tumor necrosis factor-alpha (TNF-alpha) and phorbol myristate acetate (PMA). When the reactivity of mNI-11 and mAbs binding human differentiation antigens such as CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD49d, CD50, CD54, CD58, CD80, CD102, CD106, HLA-class I, or HLA-class II antigen was compared, no mNI-11 reactivity resembling that of these mAbs was found. mNI-11 markedly induced homotypic cell aggregation of U937 cells when they were stimulated with LPS. The mNI-11-induced aggregation of LPS-stimulated U937 cells, referred to as LPS-U937 cells, required neither Fc receptor engagement nor cross-linking of the antigen defined by mNI-11 because aggregation was induced by both F(ab')2 fragments and monovalent F(ab') fragments of mNI-11. The mNI-11-induced aggregation was blocked by the addition of ethylenediaminetetraacetate, and also when incubated at 4 degrees C. mAbs to CD11a/CD18 (lymphocyte-function associated antigen-1; LFA-1) and CD54 (intercellular adhesion molecule-1; ICAM-1) completely blocked the LPS-U937 cell aggregation induced by mNI-11. The LPS-U937 cell aggregation induced by mNI-11 was partially but not completely blocked by the protein kinase C inhibitors sphingosine and H-7, and was completely blocked by the protein-tyrosine kinase inhibitor genistein. Interestingly, mNI-11 markedly promoted LPS-U937 cell adhesion to HUVECs. The mNI-11-induced LPS-U937 cell adhesion to HUVECs was not reduced in the presence of LFA-1 (CD11a/CD18) or ICAM-1 (CD54) mAbs. On the other hand, LPS-U937 cells, whether treated with mNI-11 or not, sufficiently adhered to the extracellular matrix protein fibronectin, but not to laminin or collagen type I. However, mNI-11 did not markedly promote LPS-U937 cell adhesion to fibronectin. Adhesion of LPS-U937 cells treated with mNI-11 to fibronectin was completely blocked by CD29 (beta chain of very late antigens) mAb. The surface antigen recognized by mNI-11 had a molecular size of approximately 97 kDa under non-reducing conditions and approximately 117 kDa under reducing conditions, as determined by immunoblotting analysis. We found that mNI-11 recognizes an adhesion-associated molecule distinct from any previously reported in terms of its pattern of cellular distribution and molecular weight, and also found that mNI-11 has activity which induces cell adhesion/aggregation of U937 cells when stimulated with LPS.
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PMID:Development and characterization of a novel monoclonal antibody (mNI-11) that induces cell adhesion of the LPS-stimulated human monocyte-like cell line U937. 865 55

A monoclonal antibody (mAb), designated mNI-58A, was produced by immunizing mice with the lipopolysaccharide (LPS)-stimulated monocyte-like cell line, U937. The antigen defined by mNI-58A was widely expressed on various lymphoid cells and all cell lines examined except the erythroid cell line, K562. When the reactive patterns between mNI-58A and the mAbs to various human differentiation antigens (CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD50, CD54, CD58, CD80, CD102, CD106, HLA-class I and-class II antigen) were compared, that of mNI-58A was found to be similar to those of the leukocyte function-associated antigen-1 (LFA-1) mAbs. Using a competitive immunofluorescence binding assay it was found that the preincubation with one of the CD11a mAbs, 2F12 completely blocked the subsequent binding of mNI-58A. mNI-58A prevented the homotypic cell aggregation of the phorbol myristate acetate (PMA)-activated U937 cells (referred to as PMA-U937) and PMA-activated Epstein-Barr virus (EBV)-transformed B cell lines, B-85 and Mann. mNI-58A markedly induced the spread formation of the PMA-U937 cells following this blocking of the homotypic cell aggregation, whereas 2F12 did not under the same condition. The spread formation induced by mNI-58A was completely blocked by cytochalasin B (CyB), cytochalasin D (CyD), cycloheximide (CHX) or protein kinase C inhibitors, sphingosine and H-7. The U937 cells markedly adhered to the tumor necrosis factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs) and also to the extracellular matrix protein, fibronectin, but mNI-58A did not enhance or block these adhesion process. mNI-58A precipitated two glycoproteins with molecular weight 180 kDa and 95 kDa as determined by SDS-PAGE analysis, which were identical to the LFA-alpha (CD11a) and beta (CD18) chains of leukocyte integrin precipitated by the CD11a mAbs, respectively. Sequential immunoprecipitation studies using the CD11a mAb (2F12) also indicate that mNI-58A recognizes an epitope on the alpha-chain of the LFA-1 molecule. The ability of mNI-58A to block the PMA-U937 cells and to induce the spread formation of these cells suggests that mNI-58A is a novel mAb reacting with an epitope on the alpha-chain of LFA-1 different from those recognized with the existing CD11a mAbs.
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PMID:A novel monoclonal antibody mNI-58A against the alpha-chain of leukocyte function-associated antigen-1 (LFA-1) blocks the homotypic cell aggregation and actively regulates morphological changes in the phorbol myristate acetate (PMA)-activated human monocyte-like cell line, U937. 889 74

Microglial cell activation plays a central role in acute and chronic inflammatory processes associated with neurodegeneration. As macrophage activation is generally associated with the up-regulation of specific surface antigens, the expression of CD54, and CD29 were evaluated on CD11b positive neonatal rat microglial cell cultures by flow cytometry. These cells when exposed to lipopolysaccharide, LPS, and gamma interferon, IFN gamma, exhibited a 2-3 fold increase in CD54 expression, an increase in CD29 and no change in CD11b. Maximal increases in CD54 and CD29 staining on CD11b positive microglial cells were apparent 20-24 h after LPS and IFN gamma while nitrite production reflecting inducible nitric oxide synthase activity, continued to increase. The increases in CD29 and CD54 staining were inhibited in a dose dependent manner by agents which increased intracellular cAMP levels including 100 microM 8-bromoadenosine 3':5'-cyclic monophosphate but not 8-bromoadenosine monophosphate, the phosphodiesterase inhibitor isobutyl methylxanthine and by direct activation of adenylate cyclase with forskolin. Concomitant with the dose dependent decreases in CD29 and CD54 staining were increases in intracellular cAMP and reduced TNF secretion. These results suggest that regulation of CD29 and CD54 expression on activated microglial cells involves a cAMP dependent pathway.
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PMID:Expression of CD54 (intercellular adhesion molecule-1) and the beta 1 integrin CD29 is modulated by a cyclic AMP dependent pathway in activated primary rat microglial cell cultures. 948 53

Both macrophages (MAC) and dendritic cells (DC) are members of the mononuclear phagocyte system (MPS) with monocytes (MO) as common precursor cells. Cells of the MPS are able to take up, process and present antigens to T lymphocytes, thereby inducing a primary or secondary immune response. Adhesion molecules are of crucial importance for the interaction of antigen-presenting cells with immune cells, especially T lymphocytes. By representational difference analysis, we identified CD49c (VLA-3), a member of the beta1-integrin family of adhesion receptors, as differentiation-associated antigen in MO-derived MAC. In contrast, MO-derived DC did not express CD49c mRNA. These data prompted us to compare the integrin expression pattern of MAC and DC. Both cell types showed a low expression of the alpha-chains of the beta1-integrins CD49a, CD49b, CD49d and CD49e, whereas a marked difference was observed for CD49c and CD49f. Expression of both integrins increased during MO to MAC differentiation, but was not detectable on DC. In parallel the beta1-chain (CD29) was clearly up-regulated during MO to MAC differentiation but was only weakly expressed on DC. On the other hand, the beta2-integrins CD11a, CD11b, CD11c and CD18 were all expressed on MAC and DC. Beside their role in cell-cell interaction and adhesion, beta2-integrins are also known as possible binding molecules for bacteria and lipopolysaccharide (LPS), especially for high LPS concentrations. Therefore we investigated the LPS response of MAC versus DC in terms of tumour necrosis factor-alpha (TNF-alpha) release. DC were less responsive to low doses of LPS, which can easily be explained by the very low CD14 expression on DC compared for MAC. In contrast, the TNF-alpha response was comparable to MAC when DC were stimulated with high LPS concentrations. Our results show a specific, differentiation-dependent pattern of beta1- and beta2-integrin expression on in vitro-generated MAC and DC. We suggest that the high expression of CD11/CD18 on DC could be involved in the LPS binding of DC. As LPS is not only an activation but also a differentiation stimulus for DC, the expression of CD11/CD18 on DC may be important for the successful maturation of DC and thereby the initiation of a primary immune response.
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PMID:Comparative analysis of integrin expression on monocyte-derived macrophages and monocyte-derived dendritic cells. 1092 59

Endotoxin (lipopolysaccharide (LPS), 100 ng/ml) and muramyl dipeptide (MDP 100 ng/ml), two immunomodulatory bacterial cell wall products, were incubated with human whole blood, and the expression of receptors involved in antigen presentation, costimulation, and cell activation was investigated by use of flow cytometry. On monocytes, LPS and MDP increased surface expression of human leukocyte antigen-DR (HLA-DR), CD18, CD54 (intercellular adhesion molecule-1, ICAM-1), and CD86 (B7-2). On lymphocytes, LPS but not MDP increased HLA-DR expression after 18 h. The expression of CD28, CD49d/CD29, and CD106 (vascular cell adhesion molecule-1, VCAM-1) remained unchanged on both monocytes and lymphocytes. The early increase (1-6 h) of CD18 and ICAM-1 expression led us to hypothesize that CD18-dependent costimulatory signals were involved in the later (6 h) increase of monocyte HLA-DR expression. However, blocking studies using monoclonal antibodies against CD18 (IB4, 15 microg/ml) demonstrated that the LPS- and MDP-induced increase of HLA-DR and ICAM-1 expression on monocytes was not mediated through CD18. LPS induced the expression of the early activation marker CD69 by a CD14-dependent but CD18-independent mechanism, whereas MDP did not induce CD69 expression. Analysis of leukocyte subsets demonstrated that CD4(+) T-cells, CD8(+) T-cell, CD19(+) B-cells, CD56(+) natural killer (NK)-cells, and CD14(+) monocytes increased the expression of CD69 after stimulation with LPS. Collectively, these data demonstrate a stronger immunomodulatory effect of LPS compared with MDP which may, in part, explain the established difference of toxicity between these two bacterial cell wall products.
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PMID:Endotoxin and muramyl dipeptide modulate surface receptor expression on human mononuclear cells. 1093 9

Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro secrete interleukin (IL)-6 upon 24h in co-culture. Presently, the aim was to study the mechanisms of this monocyte secretion. Paraformaldehyde (0.1% for 2min) or actinomycin-D (1 microg/ml for 24h) pre-treatment of the F-spheroids abolished the monocyte IL-6 co-culture response. Addition of glucose (100mM) or mannose (100mM), and to some extent galactose (100mM), but not fructose (100mM) to the co-cultures, partly inhibited the monocyte IL-6 co-culture response, but such addition did not inhibit the in vitro monocyte lipopolysaccharide (LPS)-generated IL-6 secretion. When mannose was added to the co-cultures, monocyte IL-6 mRNA expression was eradicated in malignant co-cultures and reduced to a low level in benign co-cultures. Addition of mouse anti-human beta(1)-integrin (anti-CD29) antibody (2 microg/ml) diminished the IL-6 co-culture response but not the monocyte LPS-generated IL-6 response. In conclusion, the monocyte IL-6 co-culture response is dependent on live spheroids and to some extent on direct contact with the F-spheroids, possibly via lectin-like receptor(s), the mannose receptor and beta(1)-integrin.
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PMID:Mechanisms for monocyte activation in co-culture with autologous tumor spheroids. 1247 63

Legionella pneumophila, the causative agent of Legionnaires' disease, is able to survive and multiply efficiently in a variety of mammalian cells. By using in vitro assays, the uptake of L. pneumophila into monocytes has shown to be mediated, at least in part, through attachment of complement-coated bacteria to complement receptors, but complement-independent phagocytosis could also be demonstrated. Since complement levels in the human lung are normally low, the role of complement-dependent phagocytosis in the pathogenesis of Legionnaires' disease is doubtful. However, the contribution of other potential phagocytosis-related host cell surface molecules to the phagocytosis of L. pneumophila has never been investigated. We therefore analyzed the role of complement receptors 1 (CD35) and 3 (CD11b/18), the lipopolysaccharide (LPS) receptor (CD14), the beta(1)-integrin chain of the fibronectin receptor (CD29), the intercellular adhesion molecule 1 (ICAM-1, CD54) and the transferrin receptor (CD71) in the complement-independent uptake of L. pneumophila. To exclude any influence of culture conditions onto phagocytosis rates, we compared a fresh clinical isolate with an agar-adapted isolate of L. pneumophila. In addition, we used three different host cell types (MM6, HeLa and Jurkat cells) expressing different rates of complement receptors. We could show that both strains of L. pneumophila were phagocytized by the three host cell lines to the same extent, but intracellular multiplication was only found in MM6 and, although to a much lesser degree, in Jurkat cells. Preincubation of MM6 cells with monoclonal antibodies directed against the above cited phagocytosis-related receptors did not result in inhibition of L. pneumophila uptake. We therefore conclude that typical phagocytosis-related cell surface receptors are not involved in the complement-independent phagocytosis of L. pneumophila.
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PMID:Investigation of mechanisms involved in phagocytosis of Legionella pneumophila by human cells. 1262 Jun 17

The alpha 4/beta 1 integrin very late antigen-4 (CD49d/CD29) is up-regulated on circulating neutrophils of septic patients. Although no individual agent mimics this effect of sepsis, we now report that following priming of human neutrophils with lipopolysaccharide or tumor necrosis factor alpha (TNF-alpha), addition of formyl-Met-Leu-Phe (fMLP) results in a "stimulated", sepsis-like, four- to fivefold rise in CD49d expression. TNF/fMLP stimulation also produced a similar increase in CD49d-mediated adhesion of neutrophils to a vascular cell adhesion molecule-1 (VCAM-1)-coated surface. Adenosine is a naturally occurring, anti-inflammatory mediator released from injured or inflamed tissues. We observed that stimulated neutrophil CD49d expression was decreased by activation of A(2A) adenosine receptors (A(2A)AR) with the selective agonist 4-[3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylicacid methyl ester (ATL146e; EC(50)=6.4 nM). ATL146e (100 nM) also reduced the fraction of stimulated neutrophils that adhered to VCAM-1 from 38 +/- 6% to 27 +/- 5%. Inhibition of CD49d expression was equally inhibited by ATL146e, added before or after TNF priming, and was reversed by incubation with the A(2A)AR-selective antagonist 4-[2-[7-amino-2-(2-furyl) (1, 2, 4)triazolo(2,3-a) (1, 3, 5)triazin-5-yl-amino]ethyl]-phenol (ZM241385; 100 nM). A suboptimal ATL146e concentration (1 nM) combined with the type IV phosphodiesterase inhibitor rolipram (100 nM) synergistically decreased stimulated CD49d expression by >50%. The cyclic adenosine monophosphate (cAMP)-dependent kinase [protein kinase A (PKA)] inhibitor H-89 (10 microM) reversed the effect of ATL146e on stimulated CD49d expression. Other means of increasing cAMP in neutrophils also decreased stimulated CD49d expression. We conclude that adenosine binding to A(2A)AR counteracts stimulation of neutrophil CD49d integrin expression and neutrophil binding to VCAM-1 via a cAMP/PKA-mediated pathway.
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PMID:Activation of A2A adenosine receptors inhibits expression of alpha 4/beta 1 integrin (very late antigen-4) on stimulated human neutrophils. 1452 68

The recruitment of monocytes appears to be a crucial factor for inflammatory lung disease. Alveolar epithelial cells contribute to monocyte influx into the lung, but their impact on monocyte inflammatory capacity is not entirely clear. We thus analyzed the modulation of monocyte oxidative burst by A549 and isolated human alveolar epithelial cells. Epithelial infection with Moraxella catarrhalis induced monocyte adhesion, transepithelial migration, and superoxide generation, whereas stimulation with lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1beta, or interferon-gamma induced adhesion or transmigration, but failed to initiate monocyte burst. The effect of microbial challenge was mimicked by phorbol myristate acetate and inhibited by the protein kinase C inhibitor bisindoylmaleimide. Furthermore, evidence for a role of platelet-activating factor-signaling in monocytes is presented. Monocyte burst was neither induced by supernatant nor affected by fixation of A549 cells, excluding the contribution of epithelium-derived soluble factors but emphasizing the mandatory role of intercellular contact. The employment of blocking antibodies, however, denied a role for the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, or CD11b/CD18 and CD49d/CD29. In essence, infection of alveolar epithelial cells with M. catarrhalis might amplify the inflammatory capacity of invading monocytes eliciting their superoxide production. The epithelial response to this microbial challenge thus clearly differed from that to proinflammatory cytokines.
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PMID:Moraxella catarrhalis--infected alveolar epithelium induced monocyte recruitment and oxidative burst. 1555 18

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