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)

We have previously shown that human bactericidal/permeability-increasing protein (BPI) is able to inhibit serum-dependent lipopolysaccharide (LPS)-mediated activation of human monocytes and neutrophils in vitro, and to counteract the lethal effects of LPS challenge in vivo. Lipopolysaccharide-binding protein (LBP) is a serum protein which participates in LPS-mediated activation of cells (Tobias, P. S., Mathison, J., Mintz, D., Lee, J. D., Kravchenko, V., Kato, K., Pugin, J., and Ulevitch, R. J. (1992) Am. J. Respir. Cell. Mol. Biol. 7, 239-245). We have proposed that BPI functions in a negative feedback loop which opposes this activation (Marra, M. N., Wilde, C. G., Collins, M. S., Snable, J. L., Thornton, M. B., and Scott, R. W. (1992) J. Immunol. 148, 532-537). We have now cloned and expressed recombinant forms of human BPI and LBP. Here we demonstrate that purified recombinant human LBP can replace the serum requirement for both LPS binding to human monocytes and LPS-mediated secretion of tumor necrosis factor alpha from these cells. These activities of LBP are inhibited by a neutralizing anti-CD14 monoclonal antibody. We further demonstrate that purified recombinant human BPI can inhibit LBP-mediated LPS binding to cells and their subsequent activation. Comparison of the LPS binding properties of BPI and LBP in enzyme-linked immunosorbent type assays and in the Limulus amebocyte lysate assay suggest that BPI has a stronger affinity for LPS than does LBP. Direct competition between BPI and LBP for LPS may explain the inhibition by BPI of the proinflammatory effects of LBP in the presence of LPS.
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PMID:Bactericidal/permeability-increasing protein and lipopolysaccharide (LPS)-binding protein. LPS binding properties and effects on LPS-mediated cell activation. 751 98

The CD14 antigen was originally described as a differentiation antigen on mononuclear cells. The purpose of this study was to investigate the relationship between the appearance of surface CD14 and the acquisition of lipopolysaccharide (LPS) responsiveness during maturation of mononuclear phagocytes. Immature THP-1 cells responded poorly to LPS in the absence or presence of serum. Treatment with the maturational agent calcitriol caused a dose- and time-dependent increase in CD14 mRNA and surface CD14 and enhanced the responsiveness of THP-1 cells to smooth and rough form LPS, complexes of LPS and lipopolysaccharide-binding protein (LBP), and LPS in low concentrations of serum. Monoclonal antibodies to CD14 blocked the responses of THP-1 to LPS, LPS-LBP complexes and LPS in serum. Immunodepletion of LBP from serum also inhibited the effect of LPS in serum. The data show that maturation of the response of THP-1 cells to LPS and LPS-LBP complexes depends on the appearance of CD14 on the cell surface. Maturation of the response to LPS in serum depends in large part on the appearance of CD14 on the cell surface and the presence of LBP in serum.
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PMID:The CD14 differentiation antigen mediates the development of endotoxin responsiveness during differentiation of mononuclear phagocytes. 751 89

Glycosyl phosphatidylinositol (GPI)-anchored membrane proteins are deficient in the blood cells affected by paroxysmal nocturnal hemoglobinuria (PNH). The relation of the deficiencies of CD59 and CD14 with the clinical features of PNH are reported. CD59 binds to complement components C8 and C9 derived from human sera and inhibits the C5b-9-mediated hemolysis in a species-selective manner. The CD59-binding sites were revealed to be localized in the alpha subunit of C8 and in the "b" domain of C9 (thrombin fragment). The deficiency of CD59 in PNH is causatively related to the hemolytic features in PNH. A monocyte differentiation antigen, CD14, is deficient in the affected PNH monocytes. CD14 is reported to be one of the receptors to lipopolysaccharide (LPS). LPS-binding to the monocytes were revealed to be mediated through CD14 on monocytes. Enhancement of LPS-binding to monocytes by the presence of serum was not seen to PNH-affected monocytes. PNH-affected monocytes showed impaired TNF-alpha production in response to LPS. The deficiency of CD14 indicates the abnormality in PNH-affected monocytes, however, its significance in the clinical features of PNH is to be clarified.
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PMID:[Clinical features and diagnosis of paroxysmal nocturnal hemoglobinuria: correlates with the deficiency of GPI-anchored membrane proteins]. 751 13

The phenotypical heterogeneity of human liver macrophages was analyzed with monoclonal antibodies that recognize antigens specific for the monocyte-macrophage lineage. Most liver macrophages in normal and diseased liver were positive for CD68, whereas fewer matured macrophages were detected by 25-F9. Comparative staining of mirror sections revealed some to be doubly positive and others to be singly CD68 positive. Quantitative analysis confirmed the difference, suggesting heterogeneity of maturation in liver macrophages. Most liver macrophages in the normal liver were negative for CD14, a receptor for lipopolysaccharide and lipopolysaccharide-binding protein complexes. Liver macrophages in liver diseases were activated to express CD14 at varying degrees and were involved in the clearance of lipopolysaccharide-lipopolysaccharide-binding protein complexes. Fc gamma RI, a receptor for monomeric IgG that is involved in antibody-mediated cell cytotoxicity, was negative in the normal liver, but was expressed in liver macrophages at inflammatory sites (e.g., in piecemeal and focal necrosis) in diseased livers. Fc gamma RII was expressed in most liver macrophages, as well as in sinusoidal endothelial cells; Fc gamma RIII was expressed in a smaller number of liver macrophages. Expression of Fc gamma RII and Fc gamma RIII was increased in chronic active hepatitis. These results suggest that liver macrophages are heterogeneous in maturation and function and that they are activated in liver diseases as shown by the novel expression of CD14 and Fc gamma RI. The restricted expression of Fc gamma RI indicates that Fc gamma RI-positive macrophages, in cooperation with cytotoxic T lymphocytes, may play an important role in liver cell injury through antibody-mediated cell cytotoxicity.
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PMID:Immunohistochemical phenotyping of liver macrophages in normal and diseased human liver. 751 62

Here we report that soluble CD14 isolated from the urine of nephrotic patients (uCD14) contains a potent cytokine inducing activity. CD14 derived from urine appeared to consist of two major polypeptides of about 54 and 48 kDa. In uCD14 isolated from three different nephrotic patients the cytokine-inducing activity appeared to co-migrate with the 48-kDa polypeptide which upon sequencing had the same N-terminal sequence as native CD14. Treatment of human monocytes and the human astrocytoma cell line U373 with uCD14 resulted in a strong secretion of tumor necrosis factor (TNF) and interleukin-6, respectively. The cytokine-inducing activity of the uCD14 preparations was unaffected by the absence of serum. This is in contrast to the activation of human monocytes and U373 cells by lipopolysaccharide (LPS) which is highly dependent on the presence of serum. The cytokine-inducing activity was not affected by LPS-binding protein (LBP) or polyclonal rabbit antibodies against LBP. The TNF-inducing activity of uCD14 was also heat labile in contrast to the cytokine-inducing activity of LPS, which was relatively heat resistant. The results suggest that CD14 may exist in at least two forms of which one is involved in cytokine induction.
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PMID:Soluble CD14 from urine copurifies with a potent inducer of cytokines. 751 94

The human B cell line RPMI 8226 exhibits variable staining with the CD14 antibody My4. We have isolated three stable clones from this line with clones 1 and 2 being My4 positive and clone 3 My4 negative. Similar to previous results in monocytes, immunoprecipitation with the My4 antibody revealed a 54-kDa cell surface molecule, analysis of supernatants showed soluble CD14, and Northern blotting demonstrated a 1.4-kb transcript in clones 1 and 2, but not in clone 3, which suggests that the My4 antibody detects CD14 in clones 1 and 2. This CD14 molecule was functional in that lipopolysaccharide stimulation induced interleukin (IL)-6 and IL-10 in clones 1 and 2 but not in clone 3. Furthermore, the My4 antibody was capable of blocking these responses at the transcript and protein levels. Finally, peripheral blood B cells were highly purified by cell sorting (> 98% CD19 positive). These cells produced IL-6 in response to lipopolysaccharide, and this response was blocked by anti-CD14 antiserum. Thus, our findings demonstrated that human B cells can express functionally active CD14.
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PMID:CD14 is expressed and functional in human B cells. 752 2

Incubation of the mouse B-lymphoma cell line 70Z/3 with bacterial lipopolysaccharide (LPS) results in the secretion of immunoglobulin M (IgM) to the cell surface. We now demonstrate that LPS rapidly induces the tyrosine phosphorylation of a 41 kDa protein in 70Z/3 cells transfected with CD14, a glycosyl phosphatidylinositol-anchored membrane receptor for complexes of LPS and LPS binding protein. There was no indication of LPS-mediated tyrosine phosphorylation in untransfected 70Z/3 cells, which do not express CD14. The 41 kDa tyrosine phosphoprotein was specifically induced by LPS, since it was not observed after incubation with another activator of IgM expression, interferon-gamma. Induction of this 41 kDa phosphoprotein was not observed when the transfected cells were treated with LPS in the absence of serum. Phosphorylation was also blocked by preincubation of the cells with an antibody to CD14. Furthermore, lipid A from Rhodobacter sphaeroides inhibited LPS-mediated tyrosine phosphorylation and surface IgM expression. Expression of CD14 in the LPS-unresponsive mutant 70Z/3 cell line 1.3E2 did not result in the secretion of IgM, although tyrosine phosphorylation was increased after incubation with LPS, suggesting that the mutation in these cells is downstream of the membrane LPS receptor.
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PMID:CD14-dependent induction of protein tyrosine phosphorylation by lipopolysaccharide in murine B-lymphoma cells. 752 Feb 84

During the course of serious bacterial infections, lipopolysaccharide (LPS) is believed to interact with macrophage receptors, resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock. CD14, a glycosylphosphatidylinositol-linked antigen, functions as an LPS signaling receptor. A critical issue concerns the mechanism by which CD14, which has no transmembrane domain, transduces its signal following LPS binding. Recently, investigators have hypothesized that CD14-mediated signaling is effected through a receptor-associated tyrosine kinase (TK), suggesting a multicomponent receptor model of LPS signaling. Wild-type Chinese hamster ovary (CHO)-K1 cells can be activated by endotoxin to release arachidonate following transfection with human CD14 (CHO/CD14). Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS-inducible responses. We sought to determine if this pathway were present in CHO/CD14 cells and to elucidate the relationship of NF-kappa B activation to the CD14 receptor system. LPS-stimulated translocation of NF-kappa B in CHO/CD14 cells resembled the same response in the murine macrophage-like cell line RAW 264.7. Protein synthesis inhibitors and corticosteroids, which suppress arachidonate release and the synthesis of proinflammatory cytokines, had no effect on translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells, demonstrating that NF-kappa B translocation is an early event. Although TK activity was consistently observed by immunoblotting extracts from activated RAW 264.7 cells, LPS-induced phosphotyrosine residues were not observed from similarly treated CHO/CD14 cells. Furthermore, the TK inhibitors herbimycin A and genistein failed to inhibit translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells, although both of these agents inhibited LPS-induced TK activity in RAW 264.7 cells. These results imply that TK activity is not obligatory for CD14-mediated signal transduction to occur in response to LPS.
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PMID:CD14-mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity. 752 Sep 14

The effect of cytokines on the proliferation and differentiation of leukemia cells from 5 patients with acute promyelocytic leukemia (APL) was examined. Interleukin-1 beta (IL-1), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) augmented uptake of 3H-thymidine into the DNA of APL cells in a dose-dependent manner in all cases. This stimulatory effect was pronounced in some, but not all, cells treated with all-trans retinoic acid (ATRA). However, nitroblue tetrazolium-reducing activity was induced in a concentration-dependent manner by ATRA in all cases. The cytokines greatly enhanced NBT reduction of APL cells treated with ATRA, and a mixture of cytokines was more effective than a single cytokine. Although GM-CSF, IL-3 and IL-1 significantly modulated the ATRA-induced morphological changes, they did not induce CD14 expression, a typical marker of monocytic differentiation. In the presence of ATRA, GM-CSF potentiated production and secretion of tumor necrosis factor-alpha (TNF) in response to lipopolysaccharide, as well as interferon-gamma which is a potent inducer of monocytic differentiation in APL cells. On the other hand, production of TNF in ATRA-treated cells was not affected by G-CSF which significantly enhanced granulocytic differentiation. The effect of cytokines on APL cell differentiation should be considered in ATRA treatment for APL patients. Potentiation of cytokine production in APL cells associated with myelomonocytic differentiation is noteworthy in the pathogenesis of "retinoic acid syndrome".
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PMID:Effect of cytokines on the proliferation and differentiation of acute promyelocytic leukemia cells: possible relationship to the development of "retinoic acid syndrome". 752 Nov 52

CD14, a glycolipid-anchored membrane glycoprotein, acts as a high affinity lipopolysaccharide receptor on leukocytes. We previously reported that the Mono-Mac-6 cell line releases two different soluble forms of CD14 (sCD14) (Labeta et al., Eur. J. Immunol. 1993. 23: 2144). Here we show that the two sCD14, which we now refer to as sCD14 alpha (low M(r)) and sCD14 beta (high M(r)), are also synthesized and released by normal human monocytes and present in normal plasma. Their mechanism of release was examined by using the Mono-Mac-6 cell line, chinese hamster ovary cell (CHO)/CD14+ transfectants and plasma from paroxysmal nocturnal hemoglobinuria (PNH) patients. It was found that: (1) sCD14 beta is released faster than sCD14 alpha and that the release of the latter is a lengthy process. (2) Monensin blocked the biosynthesis of membrane-bound CD14 (mCD14) and sCD14, additionally, a 50-kDa CD14 polypeptide accumulated in the cell lysate, suggesting that the different forms of CD14 may have a common precursor. (3) Monensin also blocked the release of sCD14 alpha from surface-labeled cells, suggesting that conversion of mCD14 to sCD14 alpha involves a mechanism of endocytosis followed by exocytosis. Interestingly, (4) sCD14 alpha and sCD14 beta were detected in PNH plasma, indicating that sCD14 alpha may also derive from an endogenous pathway. (5) Phospholipase C-released CD14 was identical in size to mCD14, thus differed from sCD14 beta by approximately 2000, indicating that release of sCD14 beta involves further processing. (6) CHO cells transfected with a CD14 cDNA coding for an eight C-terminal amino acids shorter product released an sCD14 beta-like form; thus absence of the eight C-terminal amino acids prevented mCD14 expression but not the secretion of sCD14 beta. The characterization of sCD14 alpha and sCD14 beta reported here may be useful for better understanding of variations in sCD14 levels in pathological conditions and the contribution of each sCD14 in sepsis and other, as yet unknown functions.
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PMID:The two soluble forms of the lipopolysaccharide receptor, CD14: characterization and release by normal human monocytes. 752 57


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