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 investigated the production of C3, C4, and factor B complement components in primary cultures of murine astrocytes and in clonal cell lines belonging to the astrocytic lineage by immunoprecipitation of secreted labeled polypeptides. Although C4 has not been detected, C3 appeared to be constitutively synthesized both by two transformed astroblastic cell lines and by astrocytes in primary cultures. In contrast, factor B was only secreted upon lipopolysaccharide stimulation both in astroglial primary cultures and in an immortalized astrocytic cell line. The eventual physiologic relevance of an endogenous brain production of components of the alternative pathway of complement activation is discussed.
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PMID:Primary cultures of murine astrocytes produce C3 and factor B, two components of the alternative pathway of complement activation. 365 65

Factor B, the complement alternative pathway serine proteinase, a class III gene product of the major histocompatibility complex, is a major constitutive secretion product of mouse mononuclear phagocytes. This glycoprotein was synthesized and secreted by macrophages as a doublet of Mr 90,000 and 93,000 polypeptides that were immunoprecipitable with antibodies raised to human serum factor B, and that were indistinguishable from plasma factor B by immunoreactivity, peptide mapping, and molecular weight. Macrophage factor B was cleaved and activated to factor Bb- and Ba-like fragments by factor D and cobra venom factor. Some conversion of macrophage factor B to Bb-sized fragments occurred spontaneously in the conditioned culture medium after several hours. Factor B represented approximately 0.5% of newly synthesized protein and 4-6% of the secreted protein of resident peritoneal macrophages and macrophages elicited with thioglycollate broth, pyran copolymer, NaIO4, bacillus Calmette-Guerin, or Corynebacterium parvum. We detected synthesis of factor B immediately upon explanting these macrophages in culture; synthesis continued for several days in culture. The rate of secretion of factor B, as a proportion of total protein secretion in culture, remained constant with time. By radioimmunoassay, factor B antigens accumulated in the 24-h macrophage-conditioned culture medium at 2-10 nM, and was present in cell lysates at 4-8 nmol per 10(6) cells. We detected synthesis of factor B in bone marrow-derived macrophages as early as 5 d of culture. The P388D1 macrophage line synthesized factor B, but mouse L cells did not. In contrast, apolipoprotein E, another secreted protein of macrophages, was secreted by resident and thioglycollate-elicited macrophages but not by freshly harvested pyran copolymer-activated macrophages. Its synthesis was initiated at day 9 in culture of bone marrow-derived macrophages. These data support the classification of factor B as a constitutive biosynthetic and secreted protein of immature and mature macrophages in various states of activation. Production of factor B was modulated by treatment of macrophages in vivo or in culture with bacterial lipopolysaccharide endotoxin, which increased the synthesis, secretion, and accumulation of factor B up to 11-fold.
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PMID:Factor B, the complement alternative pathway serine proteinase, is a major constitutive protein synthesized and secreted by resident and elicited mouse macrophages. 384 38

Prior absorption of normal human serum (NHS) or C2-deficient human serum (C2D) with zymosan at 0 degrees C results in diminished consumption of C3 and factor B during subsequent incubation of the sera in Mg-EGTA buffer with zymosan at 37 degrees C for 30 min. An acid eluate from the zymosan restores the defect of absorbed NHS and C2D, and also enhances C3 and factor B utilization in hypogammaglobulinemic serum (H gamma S) in a dose-dependent fashion. The activity is specific in that the eluate from zymosan fails to enhance C3 and B depletion in H gamma S or absorbed NHS by lipopolysaccharide or Sepharose. The active component of th zymosan eluate emerges from both Sepharose 4B and Sephacryl S-200 in the region of molecules with m.w. of 150,000. Absorption with protein A-Sepharose removes the activity, demonstrating that it is IgG. Digestion of the IgG with pepsin fails to diminish activity, indicating that the Fc region is not required for activity; reduction to monovalent Fab' fragments, however, abrogates activity. When IgG antibody is bound to Protein A-Sepharose, it fails to enhance C3 depletion in H gamma S by Sepharose, indicating that binding of IgG antibody by the Fab region is necessary for enhancement of alternative pathway activity in human serum.
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PMID:The role of immunoglobulins in alternative complement pathway activation by zymosan. I. Human IgG with specificity for Zymosan enhances alternative pathway activation by zymosan. 677 18

The secretion of factor B by mouse peritoneal macrophages was found to be enhanced following in vivo or in vitro stimulation with lipopolysaccharide (LPS). The intravenous administration of LPS to mice of various strains caused an increased release of factor B but not the release of acid phosphatase by the peritoneal macrophages obtained from the stimulated mice. In vitro stimulation of cultured macrophages with LPS resulted in an enhanced secretion of both factor B and acid phosphatase. The dose-dependent augmentation of factor B secretion by LPS was found in the macrophages from LPS-responsive C3H/HeN mice, whereas the macrophages from LPS-unresponsive C3H/HeJ mice did not respond to either phenol-extracted LPS or butanol-extracted LPS. The ability of LPS to cause the enhancement of factor B secretion by macrophages was abolished by alkali or acid treatment of LPS, indicating that its lipid A part was responsible for the observed effect.
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PMID:Complement proteins and macrophages. II. The secretion of factor B by lipopolysaccharide-stimulated macrophages. 690 47

Incubation of Legionella pneumophila Philadelphia 1 in normal human serum depleted of either classical-pathway component C1q or alternative-pathway component factor B resulted in activation of the complement system. Experiments focused on the role of the classical pathway in complement activation revealed that legionellae bound C1q independently of antibody. Purified preparations of L. pneumophila major outer membrane protein but not serogroup 1 lipopolysaccharide bound C1q independently of antibody. This suggests that antibody-independent binding of C1q by L. pneumophila can result in activation of the classical pathway in normal human serum and that major outer membrane protein may be a C1q acceptor on the L. pneumophila cell surface.
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PMID:Antibody-independent binding of complement component C1q by Legionella pneumophila. 759 Nov 61

This study tested the hypothesis that in vitro cleavage of C3 could be triggered with similar case in serum samples from patients with adult periodontitis (n = 26) as in samples from periodontally healthy subjects (n = 13). A lipoteichoic acid, a lipopolysaccharide and an aggregated IgG served as activators of complement. On the average, the periodontitis group generated significantly (p < 0.01) more C3d activation fragments than did the healthy group, as judged from rocket immunoelectrophoresis measurements. Cleavage of C4 and factor B were then assayed through immunoblotting, without prior purification of the sera. C4c fragments were seen in all activated samples, the healthy group causing significantly (p < 0.05) more C4 conversion than did the periodontitis group. Cleavage of factor B, taken as a measure of soluble amplification convertase formation, was about equal between the groups. We inferred therefore that the 2 groups produced comparable amounts of C3b. The results suggested, however, that periodontitis sera favour breakdown of the opsonin C3b, most likely by activating the regulatory proteins factor H and I. Lipoteichoic acid, causing moderate depletion of C4 and factor B, produced significantly (p < 0.01) more C3d fragments than the other two activators examined. It may be that complement activation is down-regulated in periodontitis sera, perhaps at the expense of adequate local opsonic function.
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PMID:In vitro cleavage of serum complement protein C3: a comparison between patients with adult periodontitis and periodontally healthy persons. 770 38

Polymyxin B (PmB), an agent often used to neutralize the effects of bacterial lipopolysaccharide (LPS), was shown to exert a dose-dependent stimulatory effect on the biosynthesis of C3, factor B, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in human monocytes. A low dose of PmB (1 to 5 micrograms/ml) efficiently suppressed the LPS-induced (1 or 100 ng/ml) production of IL-6, GM-CSF, and factor B, but not the C3 production induced by 100 ng of LPS per ml. A reduced level of GM-CSF may have contributed to the persisting high C3 concentrations and the apparent lack of LPS inhibition in the latter situation, since GM-CSF is an inhibitor of monocyte C3 biosynthesis.
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PMID:Polymyxin B stimulates production of complement components and cytokines in human monocytes. 772 27

Complement biosynthesis in monocytes is stimulated by different pathogens and modulated by a variety of cytokines, but little is known about the possible effect of transforming growth factor beta (TGF-beta) on this monocyte function. We therefore studied the effect of TGF-beta 1 and TGF-beta 2 on constitutive, lipopolysaccharide (LPS)- and Candida albicans-induced monocyte biosynthesis of complement components C3 and factor B. Under all three conditions, both forms of TGF-beta (20 ng/ml) induced a two- to fourfold increase in C3 concentration in monocyte supernatants harvested after 2 or 5 days of cell culture, an effect that was abrogated by cycloheximide. In contrast, constitutive and pathogen-induced production of factor B was suppressed by TGF-beta. The effects of TGF-beta on complement production were neutralized by a monoclonal anti-TGF-beta antibody. Moreover, TGF-beta suppressed the pathogen-induced release of granulocyte-macrophage colony-stimulating factor and down-regulated the expression of complement receptor 3 (CD11b/CD18), while the expression of CD11a/CD18, a related beta 2 integrin, was unaffected. These novel effects of TGF-beta emphasize the immunomodulatory significance of this cytokine.
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PMID:Transforming growth factor beta modulates C3 and factor B biosynthesis and complement receptor 3 expression in cultured human monocytes. 785 44

Developmental regulation of the effects of lipopolysaccharide (LPS) on complement protein biosynthesis was studied in human fibroblasts from fetuses, newborn infants and adults, and in human monocytes from newborn infants and adults, using RNA blot analysis and immunoprecipitation of metabolically radiolabelled cell lysates. The responsiveness of the third component of complement (C3) and factor B protein synthesis to LPS is limited by translational mechanisms in the newborn infant and by pretranslational mechanisms in the fetus. Translation of RNA from LPS-induced cells in a rabbit reticulocyte lysate cell-free translating system indicated no differences in specific translational activity between LPS-induced adult and neonatal RNA, suggesting that LPS-induced neonatal C3 and factor B transcripts are translationally competent, but lack either access to relevant protein synthetic pathways or co-factor(s) necessary for translation. Interferon-gamma (IFN-gamma) enhanced translational activity of LPS-induced C3 and factor B transcripts in neonatal cells, suggesting that lack of translation in these cells may be due to the absence of a necessary co-factor. Experiments with LPS and cycloheximide or LPS and interleukin-1 alpha (IL-1 alpha) suggested that a newly synthesized protein did not participate in translational regulation and that LPS induction did not alter translational activity of IL-1 alpha-induced C3 and factor B transcripts. We conclude that the responsiveness of C3 and factor B protein synthesis to LPS is regulated at developmentally unique and specific steps in gene expression.
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PMID:Developmentally regulated effects of lipopolysaccharide on biosynthesis of the third component of complement and factor B in human fibroblasts and monocytes. 792 3

In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm mode of growth. In this study we investigated the role of biofilms in activation of complement, a major contributor to the inflammatory process. Complement activation by P. aeruginosa was examined in a complement consumption assay, production of C3 and factor B conversion products assessed by crossed immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact biofilms was submaximal. Factor B conversion was of low magnitude indicating the importance of the classical pathway. Complement activation by P. aeruginosa was inhibited by polymyxin B indicating that lipopolysaccharide (LPS) was the main mediator of complement activation. Immune complexes and massive influx of neutrophils are known to cause inflammatory changes in the lungs. P. aeruginosa persisting in biofilms may contribute to the constant inflammation taking place in the lungs of CF patients.
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PMID:Complement activation by Pseudomonas aeruginosa biofilms. 801 18


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