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 role of mononuclear phagocyte-specific colony-stimulating factor (CSF-1) in human monocyte to macrophage differentiation was investigated. The addition of 1000 U/ml of CSF-1 to serum-free monocyte cultures resulted in monocyte survival comparable to that in cultures containing 5% AB serum, whereas cells in serum- and CSF-1-free medium lost their viability in 3 to 5 days. The requirement for CSF-1 coincided with the time (40 to 64 hr of culture) when the major changes in morphology and biochemical function took place in monocytes undergoing differentiation into macrophages. If CSF-1 was removed from the cultures before this time, death of the monocytes resulted. In cultures containing CSF-1, as in serum containing cultures, the lysosomal enzyme acid phosphatase was enhanced 10- to 20-fold by day 4 to 5. Superoxide production in response to phorbol myristic acetate was maintained in CSF-1 cultured monocytes, but declined with time in monocytes cultured in serum. The expression of monocyte-macrophage antigens p150.95 (LeuM5), OKM1, LeuM3, Fc receptors (32.2), and HLA-DR had increased in CSF-1 containing cultures at day 4. When antigen expression was analyzed at day 2 to 3, when cell size and 90 degrees scatter characteristics were still identical to control serum-free cultures, only p150.95, HLA-DR and FcR expression were enhanced by CSF-1. Low amounts of lipopolysaccharide (0.1 ng/ml) were found to enhance monocyte survival in the absence of added CSF-1. Lipopolysaccharide-containing cultures were found to produce CSF-1 (up to 450 U/ml, as detected by radioimmunoassay). Lipopolysaccharide (1 microgram/ml), however, did not induce enhanced expression of the maturation-related antigens. Based on these observations we conclude that CSF-1 is enhancing human monocyte survival and is involved in the events leading to the differentiation of monocytes into macrophages.
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PMID:Colony-stimulating factor-induced monocyte survival and differentiation into macrophages in serum-free cultures. 282 12

In health, pulmonary alveoli are maintained free of inflammatory responses to inhaled foreign antigens. The specific role of alveolar macrophages (AM) in modulating the local cellular immune response to antigens is controversial. Immunoregulatory function and properties of AM and blood monocytes (MN) were compared. The AM were obtained by bronchoalveolar lavage of healthy volunteers, MN by adherence of peripheral blood mononuclear cells to plastic. These accessory cells were added in increasing ratios to a responder population rendered rigorously accessory cell-dependent by nylon wool adherence and depletion of cells bearing the surface Class II MHC determinant, HLA-DR. At low ratios of mononuclear phagocytes to lymphocytes (less than or equal to 1:10), MN and AM supported significant and comparable blastogenic responses to tetanus toxoid (3H-thymidine incorporation at a 1:10 ratio was 9,697 +/- 2,508 for MN and 8,969 +/- 1,454 for AM, mean cpm +/- SE, n = 9, p = NS) and other antigens. Interleukin-1 (IL-1) activity in supernatants of MN stimulated with lipopolysaccharide (LPS), 10 micrograms/ml, was 115 +/- 28 versus 67 +/- 21 U/ml in supernatants of AM (n = 9, p greater than 0.2). At suboptimal concentrations of LPS, however, MN expressed more IL-1 activity than did AM. The specific mean fluorescence intensity of surface expression of HLA-DR determinants as assessed by flow cytometry was similar for MN and AM. At the higher ratio of 1:2, MN supported 32% increased responses to tetanus toxoid compared with that at 1:5 (p less than 0.05). In contrast, AM at a ratio of 1:2 suppressed lymphocyte response by 69% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spectrum of immunoregulatory functions and properties of human alveolar macrophages. 295 14

Antibodies directed against the human T cell receptor or the closely associated CD3 molecule stimulate polyclonal T cell proliferation via mechanisms that mimic a primary immune response. We have investigated the requirement for IL-1 production in anti-CD3 (OKT3)-mediated mitogenesis using a Hodgkin's disease cell line (L428) as the accessory cell. L428 cells did not produce detectable IL-1 following stimulation with lipopolysaccharide or phorbol ester (PMA), nor did they transcribe detectable levels of mRNA for IL-1 alpha or beta after such treatment. Despite their inability to produce IL-1, as few as 1 X 10(4) L428 cells reconstituted the proliferative response of accessory cell-depleted T cells to anti-CD3. Although larger numbers of non-rosette-forming (E-) cells were required for maximal responsiveness to anti-CD3, the maximal degree of proliferation was higher with E- cells than with L428 cells. L428-mediated T cell proliferation did not result from residual accessory cells in the responding population or an allogeneic effect since L428 cells were also capable of providing accessory cell activity for the anti-CD3-dependent generation of IL-2 by the Jurkat T cell line. Although the mechanism by which L428 cells provide accessory functions remains incompletely characterized, the ability of anti-HLA-DR F(ab')2 fragments to completely abrogate L428 and monocyte-mediated anti-CD3 mitogenesis, despite the addition of exogenous IL-1, provides evidence for the participation HLA-DR molecules in this response. These data indicate that anti-CD3-induced proliferation of unprimed human T lymphocytes can occur independently of IL-1 production by accessory cells and may involve the participation of HLA-DR molecules.
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PMID:Interleukin-1-independent activation of human T lymphocytes stimulated by anti-CD3 and a Hodgkin's disease cell line with accessory cell activity. 297 87

The biochemical events leading to enhanced membrane expression of HLA-DR and CR3 by human peripheral blood monocytes (MO) following exposure to bacterial lipopolysaccharide (LPS) were examined. In a previous study we demonstrated that an increase in intracellular calcium was necessary, but not sufficient, for MO to increase membrane expression of both antigens within 1 hr of addition of LPS. The present study was initiated to examine the other biochemical requirements which lead to the MO response to LPS. Enhanced expression of both antigens following addition of LPS was dependent on microfilament function, but independent of microtubule function and of protein synthesis. Inhibition of formation of cyclooxygenase or lipoxygenase metabolites of arachidonic acid had no effect on HLA-DR or CR3 modulation by LPS. A role for phosphatidylinositol metabolism was suggested by the inhibition of the MO response to LPS by dibutyryl cAMP and theophylline and by the enhanced expression of both antigens following addition of phorbol diesters. However, H-7, a putative inhibitor of protein kinase C, did not alter the MO response to LPS or phorbol diesters. These results suggest that LPS enhances expression of HLA-DR and CR3 by inducing redistribution of these antigens from an intracellular pool. The data also support a role for the generation of hydrolysis products of phosphatidylinositol, leading to calcium redistribution and activation of protein kinase C or other kinases, in the MO response to LPS.
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PMID:Biochemical basis of HLA-DR and CR3 modulation on human peripheral blood monocytes by lipopolysaccharide. 303 40

Bacterial lipopolysaccharide (LPS) induced human peripheral blood mononuclear cells (PBMC) to produce interferon-gamma (IFN-gamma). Monocytes play a mandatory accessory role in this process, because purified T lymphocytes failed to produce IFN-gamma in response to LPS and the addition of 2% monocytes to T cell cultures resulted in an optimal LPS-induced IFN-gamma production. IFN-gamma production was abolished in the presence of monoclonal antibodies specific for HLA-DR antigen. Addition of exogenous interleukin 2 (IL 2) markedly enhanced IFN-gamma secretion by PBMC induced with LPS. The addition of anti-Tac antibody specific for IL 2 receptors abrogated IFN-gamma production, suggesting that an interaction of IL 2 with IL 2 receptors was involved. By using a specific antibody binding assay, LPS was shown to amplify IL 2 receptor expression on PBMC, whereas exogenous IL 2 showed only a negligible enhancing effect on the expression of its own receptors. Interleukin 1 (IL 1), a product of LPS-stimulated monocytes, potentiated IL 2-induced IFN-gamma production in the absence of LPS. Neither IL 1 nor IL 2 alone induced IFN-gamma production in purified T lymphocyte cultures. When added together, however, substantial levels of IFN-gamma were induced. An enhanced IL 2 receptor expression on T cells was also demonstrated as a result of the combined action of IL 1 and IL 2. These results suggest that induction of IFN-gamma by LPS is due mainly to the generation of IL 1 and an enhanced expression of IL 2 receptors.
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PMID:Bacterial lipopolysaccharide-induced interferon-gamma production: roles of interleukin 1 and interleukin 2. 308 35

We examined the expression of HLA-DR antigen induced by mitogen, mitogen-free supernatants from mitogen-stimulated peripheral blood mononuclear cells (PBMC), or autologous and allogeneic PBMC on thyrocytes cultured for 1-2 weeks (precultured) before the addition of the stimulant. Leucoagglutinin (LAG) and concanavalin A, but not lipopolysaccharide induced HLA-DR expression on thyrocytes from normal subjects (NC) and patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). The degree of DR expression induced by LAG was significantly less in GD than in NC thyrocytes. This response was dependent on contaminating T cells, especially suppressor-cytotoxic T (Ts/c) cells, NK cells, and HLA-DR+ cells, but not helper-inducer T (Th/i) cells or B cells, in the thyrocyte cultures. OKT3 monoclonal antibody, which activates T cells specifically in the presence of monocytes, also induced thyrocyte HLA-DR expression. Furthermore, interferon-gamma (IFN-gamma) was detected in culture supernatants from LAG-stimulated thyrocytes. Anti-IFN-gamma monoclonal antibody eliminated the ability of LAG to induce HLA-DR. Mitogen-free supernatants from mitogen-stimulated PBMC also induced thyrocyte HLA-DR expression, which was inhibited by anti-IFN-gamma. The supernatants of concanavalin A- or LAG-stimulated PBMC from either untreated or recently treated patients with GD or hypothyroid HT induced less thyrocyte DR expression than NC PBMC. Indeed, the levels of IFN-gamma in supernatants from such patients were lower than those in NC, and the correlation between DR expression and IFN-gamma levels was significant. This IFN-gamma production by PBMC required Th/i cells, NK cells, and HLA-DR+ cells. Before the addition of autologous or allogeneic PBMC, only precultured HT thyrocytes expressed HLA-DR, whereas GD and NC thyrocytes did not. The induction or enhancement of DR expression on autologous thyrocytes by direct coculture with PBMC occurred within 8 days in GD and HT, but not in NC. There was a significant correlation between the serum titer of antithyroid microsomal antibodies and the degree of DR expression. Allogeneic normal PBMC also induced DR expression on NC and GD thyrocytes within 8 days, the effect on the latter being more pronounced than with autologous GD PBMC. Thyrocyte HLA-DR expression induced by autologous GD PBMC and allogeneic normal PBMC required monocytes. Th/i, and NK cells and was blocked by anti-IFN-gamma. However, the enhancement of thyrocyte DR expression by autologous HT PBMC did not require monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thyrocyte HLA-DR expression and interferon-gamma production in autoimmune thyroid disease. 309 94

A hypothetical model of the maturation pathway of Langerhans cells (LC) within an epithelial environment is presented. This model is based on in vitro studies using human gingival organ culture. In this model, T6 (CD1) antigen is induced on a T6(-) intraepithelial population by Interleukin-1 secreted by epithelial cells. This process is abrogated by a locally produced Interleukin-1 inhibitor, ILS. These T6(+) LC then express first HLA-DR and subsequently HLA-DQ surface antigens under the influence of either lipopolysaccharide or gamma interferon. The induction of these Class II antigens on LC is inhibited by prostaglandin E2. It is postulated that these Class II antigen positive LC are then available to function as antigen presenting cells. This hypothesis is consistent with in vitro studies and several in vivo observations. The basis of the hypothesis is the demonstration that locally produced factors may exert an influence on LC behaviour within an epithelial environment.
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PMID:The regulation of Langerhans cell T6, DR and DQ antigen expression: an hypothesis. 313 9

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

Homologous human macrophage hybridoma cell lines were obtained by somatic cell fusion between peripheral blood monocyte-derived macrophages and a subclone of the myelomonocytic cell line, U937-F9. The hybridoma cell lines grown in vitro for more than a year were confirmed by manifestations of phagocytosis, adherence, nonspecific esterase, acid phosphatase, chromosome numbers and other cell surface antigens. Cell surface antigens on hybridomas were detected by flow cytometry analysis with monoclonal antibodies. With interclonal differences, a typical phenotype of hybridoma cells was CDw14+, OKM5+, Mac-1+ (equivalent to OKM1 and Mol), OKT9+, HLA-DR- and CD20+. After stimulation with lipopolysaccharide and calcium ionophore A23187, culture supernatants of clones c18A and c29A showed cytotoxic activity against human melanoma A375 Met-Mix and other cell lines which were resistant to the tumor necrosis factor, lymphotoxin and interleukin 1. This cytotoxic factor was found to be distinct from the tumor necrosis factor, lymphotoxin and interleukin 1 using the anti-tumor necrosis factor, anti-lymphotoxin and anti-interleukin 1 antisera.
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PMID:Homologous human macrophage hybridomas that produce a novel cytotoxic factor in their culture supernatants. 328 4


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