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)

CD14 has been reported to be the lipopolysaccharide (LPS)-LPS binding protein receptor. The effects of interferon-gamma (IFN-gamma) on CD14 expression have not been clearly established. The purpose of this investigation was to examine the effects of IFN-gamma alone and IFN-gamma followed by bacterial LPS on CD14 expression. Human peripheral blood monocytes were isolated by counterflow centrifugal elutriation (CCE). Monocytes were cultured for 48 h with IFN-gamma alone or for 24 h with IFN-gamma followed by LPS for a second 24 h. IFN-gamma alone caused a down-regulation of CD14 expression, as assessed by flow cytometry, relative to CD14 expression in untreated monocytes. In addition, CD14 expression was even more significantly down-regulated after IFN-gamma pretreatment followed by either Prevotella intermedia or Salmonella typhimurium LPS. Likewise, the percentage of CD14+ monocytes decreased after IFN-gamma alone and even more dramatically after IFN-gamma treatment followed by either LPS. This study clearly demonstrated that IFN-gamma down-regulates CD14 expression and that LPS following IFN-gamma pretreatment potentiates this effect.
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PMID:The effects of interferon-gamma and bacterial lipopolysaccharide on CD14 expression in human monocytes. 143 9

The immunomodulatory hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to suppress T-cell proliferation and interleukin-2 synthesis as well as B-cell immunoglobulin synthesis, while stimulating many macrophage functions. We have previously shown increased synthesis of interleukin-1 beta in lipopolysaccharide (LPS)-stimulated U937 cells after pretreatment with 10 nmol/L 1,25-(OH)2D3. We now show that 1,25-(OH)2D3 also primes the increase in U937 cell tumor necrosis factor (TNF)-alpha-accumulated mRNA after activation with LPS; 50% effective concentration (EC50) for the LPS-induced expression of TNF-alpha mRNA was decreased by two orders of magnitude after incubation with 10 nmol/L 1,25-(OH)2D3. Pretreatment of U937 cells with 10 nmol/L 1,25-(OH)2D3 also increased subsequent LPS-induced TNF-alpha mRNA expression by twofold and cell-associated TNF protein levels by more than ninefold. This potentiation was steroid-specific for 1,25-(OH)2D3 because dexamethasone inhibited TNF-alpha mRNA. The potentiation required prior exposure to 1,25-(OH)2D3 for more than 6 hours and was clearly seen after 12 hours. The finding that the sensitivity of the U937 cell monokine response to LPS was dramatically increased by 1,25-(OH)2D3 and the delayed effect on the LPS-stimulated TNF-alpha gene transcript levels indicated that 1,25-(OH)2D3 may be altering the expression of a protein(s) in the U937 cell LPS-signal transduction pathway. In fact, 1,25-(OH)2D3 induced expression of the mRNA for CD14, the high affinity, cell-surface glycoprotein receptor for LPS, which could account for the enhancement of LPS-stimulated monokine gene expression by 1,25-(OH)2D3. Thus, local monokine gene expression may be regulated by both the amount and the temporal entry of the vitamin D hormone and activator(s) into the inflammatory microenvironment.
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PMID:Potentiation of lipopolysaccharide-induced tumor necrosis factor-alpha expression by 1,25-dihydroxyvitamin D3. 145 Apr 7

The expression of adhesion molecules in monocytes of patients with recent onset type I diabetes was analysed. Monocytes were identified as CD14-positive cells by flow cytometry. The percentage of monocytes expression LFA-1 alpha, ICAM-1 and HLA-DR was slightly lower in recent onset type I diabetes (n = 13) compared to normal subjects (n = 15) and was significantly decreased after activation of cells with lipopolysaccharide and interferon-gamma for 5-24 hr. Receptor densities on adhesion molecule-positive monocytes and the expression of LFA-1 beta were normal. These data indicate that monocyte trafficking is abnormal in recent onset type 1 diabetes.
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PMID:Decreased expression of adhesion molecules on monocytes in recent onset IDDM. 167

Leukocytes respond to lipopolysaccharide (LPS) at nanogram per milliliter concentrations with secretion of cytokines such as tumor necrosis factor-alpha (TNF-alpha). Excess secretion of TNF-alpha causes endotoxic shock, an often fatal complication of infection. LPS in the bloodstream rapidly binds to the serum protein, lipopolysaccharide binding protein (LBP), and cellular responses to physiological levels of LPS are dependent on LBP. CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS. Thus, LPS may induce responses by interacting with a soluble binding protein in serum that then binds the cell surface protein CD14.
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PMID:CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. 171 34

Tumor necrosis factor alpha, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, and formyl peptide were each found to cause a twofold increase in expression of CD14 on the surface of polymorphonuclear leukocytes (PMN). Upregulation of CD14 was complete by 20 min and thus appeared to result from expression of preformed stores of protein. The CD14 on the surface of PMN was shown to serve two biological functions. It bound particles coated with complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP). This binding activity was enhanced by agonists that upregulated CD14 expression and may serve in the clearance of Gram-negative bacteria opsonized with LBP. Interaction of CD14 with LPS in the presence of LBP or serum also caused a dramatic, transient increase in the adhesive activity of CR3 (CD11b/CD18) on PMN. Enhanced activity of CR3 and other members of the CD11/CD18 family underlies many of the known physiological responses of PMN to LPS and may be a central feature of the in vivo responses of PMN to endotoxin.
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PMID:Activation of the adhesive capacity of CR3 on neutrophils by endotoxin: dependence on lipopolysaccharide binding protein and CD14. 170 13

We have previously cloned the murine homolog of cDNA for the human myelomonocytic differentiation antigen, CD14. We synthesized three hydrophilic peptides derived from the predicted amino acid sequence of murine CD14 (mCD14), designated MS7.1, MS7.2, and MS7.3, respectively, and raised antisera against them. Each antiserum showed specific reactivity to the same peptide used for immunization. One of the anti-mCD14 antisera directed against MS7.3 peptide (AMS7.3) demonstrated the highest titer and definitively reacted with monocytic cell lines, inflammatory polymorphonuclear cells, and macrophages. Significant cross-reactivity of AMS7.3 was observed in the human monocytic cell line, THP-1. COS-1 cells transfected with MS7 cDNA expressed an antigen recognized by AMS7.3. Resident peritoneal and alveolar macrophages both expressed mCD14. mCD14 expression in peritoneal but not alveolar macrophages increased after treatment with lipopolysaccharide. Expression of mCD14 varied among monocytic cell lines and roughly paralleled the mRNA levels except in MI cells. SDS-PAGE and isoelectric focusing analysis of immunoprecipitated mCD14 showed that mCD14 was a 53 kd disulfide-linked protein with a pI of 4.5-5.1. Reduction of molecular weight by endo F treatment demonstrated that mCD14 was an N-linked glycoprotein. Since mCD14 is shed from the cell surface membrane by phosphatidylinositol-specific phospholipase C treatment, the indication is that mCD14 is a phosphatidylinositol-linked protein. The soluble form of mCD14 was detectable. Treatment with anti-mCD14 before interferon gamma (IFN gamma) stimulation significantly enhanced IFN gamma-induced H-2 antigen expression in the macrophage cell line.
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PMID:Molecular and physiological properties of murine CD14. 170 50

Recent studies have identified three classes of receptor molecules involved in recognition of endotoxin. Two classes of receptors, the CD18 antigens and the scavenger receptor, recognize lipopolysaccharide directly and function principally in its catabolism. A third molecule, CD14, recognizes lipopolysaccharide with the aid of a serum protein, lipopolysaccharide-binding protein, and may be a principal mediator of secretory responses of leukocytes.
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PMID:Multiple receptors for endotoxin. 171 27

Recently it has been demonstrated that the CD14 molecule which is expressed on monocytes and macrophages serves as a receptor for lipopolysaccharide (LPS) bound to LPS-binding protein (LBP) and thus mediates LPS-induced tumour necrosis factor (TNF) production. Here we report that CD14 is found as a soluble (s) molecule in serum. In healthy volunteers sCD14 levels (mean +/- s.e.m.) were 3.7 +/- 0.05 micrograms/ml (n = 30, 25-50 years of age) as determined by ELISA (detection limit 20 ng/ml serum) using two monoclonal antibodies in a sandwich technique. In polytraumatized patients (n = 16) significantly decreased levels (1.7 +/- 0.3) were detected immediately after the trauma, which increased to 4.9 +/- 0.3 micrograms/ml within the first 6 days post trauma. sCD14 remained elevated during the first 14 days post trauma in patients with the most severe injuries (injury severity score greater than 45 points), whereas a return to normal levels was observed in patients with an injury score of less than 45 points. In addition, the levels of the high-density lipoproteins that partially inactivate free endotoxin are significantly decreased post trauma. No correlation between parameters of inflammation (C3a and neopterin levels, leucocyte counts, amount of band cells), liver function and sCD14 levels was established. Comparable to polytraumatized patients, increased sCD14 serum levels were observed in five patients with burn trauma (burned area greater than 35%) within the second week post trauma when clinical signs of septicaemia were evident.
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PMID:Serum CD14 levels in polytraumatized and severely burned patients. 171 13

The 52 kD myeloid membrane glycoprotein CD14 represents the receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP); it is involved in LPS induced tumor necrosis factor-alpha production. Expression of CD14 increases in monocytes differentiating into macrophages, and it is reduced by rIFNg in monocytes in vitro. In the present study CD14 membrane antigen expression was investigated in cultures of human mononuclear leucocytes (PBL), in elutriated, purified monocytes, and in blood monocyte derived Teflon cultured macrophages. Cells were incubated for 15 or 45 h with rIL-1, rIL-2, rIL-3, rIL-5, rIL-6, rTNFa, rGM-CSF, rM-CSF, rTGFb1, rIFNa, lipopolysaccharide (LPS), and, as a control, rIFNg. The monoclonal antibodies Leu-M3 and MEM 18 were used for labelling of CD14 antigen by indirect immunofluorescence and FACS analysis of scatter gated monocytes or macrophages. IFNg concentrations were determined in PBL culture supernatants by ELISA. rIFNa and rIL-2 reduced CD14 in 15 and 45 h PBL cultures, an effect mediated by endogenous IFNg, since it was abolished by simultaneous addition of an anti-IFNg antibody. rIFNa and rIL-2 were ineffective in purified monocytes or macrophages. rIL-4 strongly reduced CD14 in PBL and purified monocytes after 45 h, whereas in macrophages the decrease was weak, although measurable after 15 h. The other cytokines investigated did not change CD14 antigen expression. Cycloheximide alone reduced CD14, but when added in combination with rIFNg the effect on CD14 downregulation was more pronounced. The effect of rIFNg on CD14 in PBL cultures was dose-dependently inhibited by rIL-4 and this inhibition is probably due to an IL-4 mediated blockade of IFNg secretion. LPS at a low dose increased CD14, at a high dose it produced a variable decrease of CD14 in PBL, which was probably due to LPS induced IFNg secretion. LPS strongly enhanced CD14 in 45 h cultures of purified monocytes. The results, showing that CD14 antigen expression is upregulated by LPS and downregulated by rIFNg and rIL-4, suggest that the LPS-LBP receptor is involved in the feedback response of IFNg and IL-4 to LPS stimulation.
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PMID:Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages. 172 47

Morphological and functional characteristics of a permanent human leukemia cell line (DD) that possesses myelomonocytic features were investigated. The cells bear a second type Fc gamma receptor and form rosettes with sheep erythrocytes sensitized with rabbit IgG (EA). However, the surface-bound EA is not internalized. The cell line lacks the surface markers CD2, CD19, CD14, HLA-DR, Fc gamma receptor I, Fc gamma receptor III, and CR3. alpha 1-Antitrypsin, lysozyme, Factor XIII a subunit of blood coagulation, and acid phosphatase reactions were negative. A terminal differentiation of the DD cell line was observed when the expression of CD14, CR3, Fc gamma receptor I, and Fc gamma receptor III was induced. The DD cells induced with 12-O-tetradecanoylphorbol-13-acetate or Escherichia coli lipopolysaccharide can internalize EA via Fc gamma receptor II and complement-coated yeast in the function of the inducers. The phagocytic ability appears to be parallel with the appearance of enzymes which participate in phagocytosis.
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PMID:Marker profile, enzyme activity, and function of a human myelomonocytic leukemia cell line. 173 17


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