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 secretions of interleukin 1 (IL-1), tumour necrosis factor alpha (TNF), and prostaglandin E2 (PGE2) of low-dose E. coli lipopolysaccharide (LPS)-stimulated human monocytes (M phi) were investigated in an endotoxin (ET)-free milieu (less than 1.6 pg LPS/ml). Human M phi cultures from nine healthy men were stimulated with 0, 12.5-500, and 250,000 pg LPS/ml as measured by a very sensitive Limulus test. The IL-1 activity was tested by the mouse costimulatory thymocyte (LAF) assay, which was thoroughly standardized and characterized (interassay variation 22-24%, intra-assay variation 3-7%). Spontaneous M phi secretions of IL-1, TNF, and PGE2 were negligible, but 12.5 pg LPS/ml significantly stimulated the secretions of these M phi products and the monokine responses to 500 and 250,000 pg LPS/ml were almost in the same range. It was demonstrated that the secretions of IL-1-TNF and TNF-PGE2 were strongly correlated. Pronounced interindividual differences in LPS responsiveness were demonstrated, and two low-responders, one of whom was HLA-DR1,2-positive, were identified. Three first-degree relatives of the DR1,2-positive low-responder had similar low responses. Furthermore, M phi cultures were prepared weekly for 4 weeks from four HLA-DR different men and the only DR2,2 homozygous individual had low monokine responses. In conclusion, stable interindividual differences in in vitro monokine and PGE2 secretions of LPS-stimulated M phi were demonstrated. It is suggested that HLA-DR2-positive individuals may be low responders.
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PMID:Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. 326 Jun 83

The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysaccharide-activated mononuclear cells from 39 healthy donors was studied in vitro by bioassay and ELISA. The donors were typed for HLA-A, -B, -C, -DR, and -DP antigens. There was no detectable production of TNF beta (lymphotoxin). The intracellular levels of bioactive TNF alpha were minimal or undetectable in all cases. Cells from HLA-DR2+ individuals secreted significantly lower amounts of TNF alpha than cells from HLA-DR2- donors [2 ng/ml (1.5-4.4) and 7.5 ng/ml (3.9-8.3) respectively (medians 25-75%); P less than 0.01]. The difference disappeared if the cells were preactivated for 2 days with 1000 U/ml of recombinant gamma interferon (rIFN-gamma). In some individuals, the TNF alpha response increased considerably after IFN-gamma priming, in particular in those possessing the HLA-DR2 antigen. In contrast, there was no detectable difference in the production of IL-1 beta between the donors, and the IL-1 beta response decreased significantly after rIFN-gamma priming in HLA-DR2+ individuals [2.3 ng/ml (1.1-8.4) versus 7.2 ng/ml (5-7.9); P less than 0.05] and in HLA-DR2- individuals [3 ng/ml (1.1-5.3) versus 5.7 ng/ml (3.9-7.5); P less than 0.01]. There was no correlation between the TNF alpha and IL-1 responses and any of the other HLA-DR, -DP, or -B antigens. There was a significant positive correlation between the levels of TNF alpha measured by ELISA and by cytotoxicity assay. However, the TNF alpha-containing supernatants from 9 out of 37 individuals appeared to contain inhibitor(s) of the biological activity of TNF alpha. The presence of inhibitor(s) was not associated with any HLA antigens.
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PMID:Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide. 326 32

The production of procoagulant activity by circulating monocytes and its regulation by a cytokine secreted by mitogen-stimulated peripheral blood mononuclear cells was investigated in recipients of HLA-identical sibling bone marrow transplants. Blood monocyte numbers reached the normal range within 3 weeks of transplant. After stimulation with lipopolysaccharide, macrophage procoagulant activity was found to be within the normal range in all patients at all times post transplant. It did not appear to correlate with the presence or absence of graft-versus-host disease. Surprisingly, and in marked contrast to our previously documented severe depression of interleukin 2 production by transplant recipients' peripheral blood mononuclear cells, the mitogen-induced production of the cytokine that induces procoagulant activity production (macrophage procoagulant inducing factor, MPIF) was also normal in the majority of patients when assayed using the responsive myelomonocytic cell line RC-2A. These findings suggest firstly that monocyte differentiation and function normalize rapidly post transplant; and secondly, when taken together with previous studies, that the ability of peripheral blood mononuclear cells to synthesize cytokines post transplant varies greatly according to the specific cytokine involved.
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PMID:Cytokine activity after human bone marrow transplantation. II. Production of macrophage procoagulant activity and the cytokine regulating its production, macrophage procoagulant inducing factor. 329 28

Activation of T cells requires three signals from an antigen-presenting cell: antigen, Ia determinants (HLA-D region determinants in man), and interleukin 1 (IL-1). Recent evidence has suggested that macrophages, dendritic cells, epidermal Langerhan's cells, and endothelial cells can each function as antigen-presenting cells (APC). If these cell types can independently function as APC, they should synthesize Ia determinants and secrete IL-1. To determine if endothelial cells fulfill these requirements, we have propagated human umbilical vein endothelial cells by serial subculture for extended periods of time and assessed Ia expression and IL-1 secretion. The endothelial cells were subcultured for 8 months (approximately 20 subcultures) and were found to display classic morphology and immunofluorescent staining for the endothelial cell-specific marker Factor VIII-related antigen. In a separate paper we have shown that these subcultured endothelial cells can present antigen to T cells in a HLA-D region-restricted fashion (C. R. Wagner, R. M. Vetto, and D. R. Burger, Subcultured human endothelial cells can independently function as fully competent antigen-presenting cells, accepted for publication, Hum. Immunol.). In this paper we present evidence demonstrating that extensively subcultured endothelial cells biosynthesize both HLA-DR and HLA-DS molecules after exposure to T cells and antigen or to a supernatant from antigen-activated T cells. Evidence is also presented that when endothelial cells are cultured in the presence of lipopolysaccharide they secrete a molecule(s) with IL-1 activity as assayed by LBRM-33-IA5 cell line production of interleukin 2.
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PMID:Expression of I-region-associated antigen (Ia) and interleukin 1 by subcultured human endothelial cells. 387 91

Reactive arthritis is usually self-limiting polyarthritis, which develops after certain gastrointestinal or urogenital tract infections, mostly in susceptible HLA B27-positive individuals. In the pathogenesis of this arthritis, it is probably important that structures of the causative bacteria are found in the affected joints. The structure found in the synovial fluid phagocytes of the patients with reactive arthritis after Yersinia, Salmonella, and Shigella infections has always been lipopolysaccharide (LPS) of the causative bacteria. It has been in a highly processed form but still immunoreactive. To follow the degradation process of LPS, we fed peripheral blood monocytes of healthy blood donors with heat-killed Yersinia enterocolitica O:3 bacteria in vitro and monitored the fate of LPS by immunofluorescence and immunoblotting methods. Heat-killed bacteria were used since Y. enterocolitica O:3 bacteria are able to live inside monocytes in vitro and dividing intracellular bacteria would have made it impossible to monitor the degradation process of LPS with these methods. Both the core region and the O-polysaccharide chain of LPS persisted in cytoplasmic vacuoles and on plasma membrane of monocytes through the 7-day follow-up time. Migration properties of processed LPS in sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggested structural modifications of LPS. We also demonstrated that core epitopes appearing on the surface of Yersinia-fed monocytes on day 4 of incubation were processed intracellularly, suggesting that LPS-containing phagocytes are a constant source of membrane-active LPS in their microenvironment as well as in the joints of arthritic patients.
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PMID:Yersinia lipopolysaccharide is modified by human monocytes. 769 97

We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. No correlation with TNF-beta secretory capacity was found for any of the markers studied. TNF genotyping allowed us to define four extended HLA haplotypes which correlate with TNF-alpha secretory capacity. Two of these are DR4 positive: DQw8, DR4, TNFB*1, TNFa6, B44, A2 and DQw8, DR4, TNFB*2, TNFa2, B15, A2. Individuals carrying the TNFB*2, TNFa2 haplotype had a higher TNF-alpha secretory capacity than those carrying the TNFB*1, TNFa6 haplotype. In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM.
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PMID:Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. 809 42

Several studies have implicated tumor necrosis factor (TNF)-alpha in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In the present study we analyzed the first reported TNF-alpha gene polymorphism in relation to IDDM. We have made frequence analysis and tested in vitro lipopolysaccharide (LPS)-induced TNF-alpha secretion. A significant difference in allele frequency was observed between patients and controls (p = 0.03). However, a very strong association of the uncommon TNF2 allele was observed with the HLA-B8, -DR3 alleles. The relative risk (RR) of TNF2 was 2.2 compared to a RR of 3.1 for DR3. One reason for this difference was the identification of the TNF1 allele on the otherwise strongly IDDM-associated HLA-DR3 haplotype: DQB1*0201, DQA1*0501, DRB1*0301, TNFc2, TNFB*2, TNFa1, TNFb5, B18. Thus, the IDDM-associated TNF2 allele had no DR3-independent value as a disease marker. The LPS-induced TNF-alpha production by human monocytes in relation to genotypes demonstrated that TNF1/2 heterozygous individuals had higher, though not statistically significantly (p = 0.08) levels than TNF1-homozygous subjects. However, this difference was rather small, unlikely to be of biological significance and based on the present material we cannot establish the functional importance of this polymorphism.
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PMID:No independent association between a tumor necrosis factor-alpha promotor region polymorphism and insulin-dependent diabetes mellitus. 822 82

Normal volunteers received single doses of recombinant human interleukin-10 (rhIL-10; n = 6 per group) or placebo (n = 3 per group) by intravenous injection to characterize pharmacokinetics, tolerability, and immunomodulatory effects. Dosages were 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 micrograms/kg. Dose-related adverse effects consisted of a mild-to-moderate flu-like syndrome characterized by fever with chills, headache, and myalgias at the highest dose. The mean terminal phase t1/2 ranged from 2.3 +/- 0.5 to 3.7 +/- 0.8 hours. Dose-related effects of rhIL-10 included transient increases of circulating neutrophils and monocytes and decreases of lymphocytes. rhIL-10 markedly suppressed, in a time- and dose-dependent manner, the synthesis of the inflammatory cytokines IL-1 beta and tumor necrosis factor alpha by whole blood stimulated ex vivo with bacterial lipopolysaccharide. Circulating numbers of CD14+/HLA-DR+ cells at 24 hours after the dose were increased in a dose-dependent manner. Effects on expression of HLA-DR by CD14+ cells were variable. There was no apparent effect on HLA-DR expression by CD20+ cells. The immunomodulatory effects of rhIL-10 merit further clinical investigation.
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PMID:Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers. 855 93

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


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