Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of polyclonal antibodies to mouse serum components on the primary humoral immune response of mice in vivo were studied. It was observed that rabbit IgG to complement component C3 and albumin and mouse IgG to C5, but also heat-aggregated non-immune rabbit IgG, enhanced the agglutinating antibody response to sheep erythrocytes (SRBC). Since the increase in response was only observed when antigen and antibodies were administered via the same route (i.p.), immunological adjuvant activity was implicated. Ineffectiveness of anti-C5 IgG in C5-deficient mice indicated that the antibody-induced adjuvant activity is mediated by in vivo formed immune complexes (IC). The adjuvant activity of IC was reduced by selective C3-depletion of animals, pointing to a requirement of C3. The effect of variations in other parameters was studied with anti-C3 and anti-C5 IgG as immunoadjuvant. The immunostimulatory effect was most pronounced when the antibodies were administered simultaneously with or shortly before antigen. Treatment of animals with antibodies one or two days before antigen, however, resulted in a suppression of the response. The response to thymus-independent antigens was not enhanced by anti-C3 nor by anti-C5 IgG. Optimal adjuvant activity of anti-C3 IgG was observed at low antigen doses. Nude mice were insensitive to the immunopotentiating effect of anti-C3 and so was the F1 progeny of BALB/c male and CBA/N female mice expressing a B-cell maturation defect. C5 deficiency and lipopolysaccharide (LPS) non-responsiveness did not affect the adjuvant activity of in vivo formed C3-anti-C3 IC.
 ...
PMID:C3- and T-cell-dependent adjuvant activity of in vivo formed immune complexes. 187 75

Salmonellae differing in the O-antigen side chain of their lipopolysaccharide were previously shown to activate the alternative pathway of complement to different extents. We now examine the generation of the major cleavage fragment of the complement component C3 (C3b) on these bacteria in a system that contains the purified components C3, B, D, and P but lacks the regulatory proteins H and I. The deposition of C3b in this system reproduces the same pattern obtained earlier with the use of whole serum, with the expected differences among the strains bearing different O-antigen. However, two distinct mechanisms for these differences in C3b generation became apparent. The intermediate activating strain showed 3 to 4 times less initial deposition of C3b than the other two strains. In contrast, the least activating strain showed adequate initial deposition but poor amplification, as shown by 2 to 3.4 lower amplification indexes as compared with those on the other two strains. Binding studies with factor B showed that decreased C3 convertase formation was responsible for the low amplification on this strain. Only 25% of the C3b bound to its surface was able to bind factor B with a high affinity, in comparison with 90% on the other two strains. No differences were found for the binding of factor H among the strains. These studies identify the molecular mechanisms by which these bacteria avoid complement activation.
 ...
PMID:C3b generation is affected by the structure of the O-antigen polysaccharide in lipopolysaccharide from salmonellae. 244 Sep 49

The purpose of this study was to obtain additional information on the mechanism by which interferon-gamma (IFN-gamma) is able to regulate gene expression in macrophages. The expression of the genes for class II histocompatibility I-A beta, tumor necrosis factor (TNF) and complement component C3 was assayed after treating bone marrow macrophages with IFN-gamma. Each gene displayed a characteristic pattern of regulation. First, the increase in the level of RNA for each gene followed different kinetics. The level of TNF RNA increased within 15 min after IFN-gamma treatment and reached a plateau after 4 h. In contrast, there was a lag of about 4 h before the level of I-A beta RNA began to rise and a plateau was not reached until 48 h after the IFN-gamma treatment began. C3 gene expression followed an intermediate time course between that for TNF and I-A beta. Second, the expression of I-A beta was inhibited when cells were treated with both IFN-gamma and cycloheximide, while the expression of TNF and C3 was not. Interestingly, the sensitivity to cycloheximide only lasted 30 min following the addition of IFN-gamma, after which cycloheximide had no effect on the expression of I-A beta. Third, lipopolysaccharide abolished the IFN-gamma-induced expression of I-A beta, but enhanced the expression of TNF. Based on these observations, we conclude that IFN-gamma must activate multiple pathways to regulate gene expression in macrophages.
 ...
PMID:Interferon-gamma activates multiple pathways to regulate the expression of the genes for major histocompatibility class II I-A beta, tumor necrosis factor and complement component C3 in mouse macrophages. 250 20

Secretion of complement component C3 by the mouse macrophage-like cell lines PU5-1.8, J774A.1, RAW264.7, and P388D1 was measured using an enzyme-linked immunosorbent assay for mouse C3. All cell lines secreted antigenically detectable C3 with the relative secreted C3/10(6) cells/24 h ranked as J774A.1 greater than P388D1 greater than or equal to PU5-1.8 much greater than RAW264.7. C3 secretion was enhanced two- to fourfold in cultures of all cell lines when treated with lipopolysaccharide, streptococcal cell walls, or lymphokine-containing supernatant fluids of mitogen-stimulated spleen cells. A differential induction of C3 synthesis and secretion was indicated since secreted lysozyme and total cellular protein were not elevated in a manner comparable to C3. The relative inducibility of cell lines for C3 secretion in either lipopolysaccharide- or cell wall-treated cells could be ranked as PU5-1.8 greater than P388D1 greater than J774A.1 greater than RAW264.7. C3 secretion was inhibited by cycloheximide or hydrocortisone. Mouse macrophage-like cell lines retain baseline and inducible C3 synthetic activities as do normal macrophages and can serve as homogeneous cultures in which to study regulation of complement biosynthesis.
 ...
PMID:Complement component C3 secretion by mouse macrophage-like cell lines. 347 27

Sub-microgram quantities of bacterial lipopolysaccharide (LPS) have been found to substantially reduce the intracellular catalytic activities of three representative lysosomal enzymes (namely, acid phosphatase, hexosaminidase, and beta-glucuronidase) in human monocyte-derived macrophages. This response was not associated with a concurrent increase in enzyme catalytic activity in the culture supernatant, and hence, could not be explained by mobilization of preformed material. By conducting experiments in the presence and absence of indomethacin, a cyclooxygenase inhibitor, the reduction in lysosomal enzyme catalytic activities was shown not to be dependent on the ability of LPS to induce prostaglandin E2 production. The response was not found to be the result of a more generalized LPS-dependent reduction in the ability of the cells to synthesize protein, since the presence of LPS in macrophage cultures did not appreciably affect the amount of [35S]methionine incorporated into total cellular proteins. A kinetic analysis of the effect of LPS on the down-regulation of enzyme catalytic activities indicated that this was an early response of the cells to LPS exposure. An investigation of the effects of blockade of enzyme catabolism (using the lysosomotropic weak-base, methylamine) indicated that the reduction of catalytic enzyme activities in response to LPS was probably due to a decreased rate of production of active product, rather than an enhanced rate of enzyme catabolism. This suggestion was confirmed by experiments in which the synthesis of pro-hexosaminidase (measured by biosynthetic labeling with [35S]methionine and specific immunoprecipitation of labeled pro-hexosaminidase) was found to be reduced by 42% after a 24-h exposure to LPS (although the synthesis of complement component C3 was stimulated by a factor of 4.5). It is suggested that the ability of LPS to regulate the functional expression of protein products contributes to changes in the overall functional status of these cells in response to this bacterial product.
 ...
PMID:Bacterial lipopolysaccharide suppresses the production of catalytically active lysosomal acid hydrolases in human macrophages. 370 Apr 68

We determined the effect of thermal injury on the in vitro production of the immunoactive substances tumor necrosis factor, interleukin 1, prostaglandin E2, and complement component C3 by lipopolysaccharide-stimulated guinea pig bone marrow macrophages and on the cytotoxicity of these cells. Macrophages from burned animals produced different amounts of these mediators compared with unburned animals at certain culture times, suggesting that thermal injury could program the bone marrow cells to respond differently from normal cells to in vitro stimulation with lipopolysaccharide. Also, the macrophages from burned animals displayed greater cytotoxicity towards L929 target cells. These results suggest that there is a complex interaction among cellular secretory products, especially after thermal injury, that may be important in host defense.
 ...
PMID:The activation of bone marrow macrophages 24 hours after thermal injury. 841 87

Previous studies indicate that sialylation of lipopolysaccharide (LPS) by host CMP-N-acetylneuraminic acid (CMP-NANA) catalyzed by bacterial sialyltransferase rendered gonococci resistant to killing by phagocytes, to entry into epithelial cell lines, to killing by immune serum and complement, and to absorption of complement component C3. These results have been confirmed by comparing a sialyltransferase-deficient mutant (strain JB1) with its parent (strain F62) in appropriate tests. In contrast to F62, JB1 was very susceptible to killing by human polymorphonuclear phagocytes in opsonophagocytosis tests and incubation with CMP-NANA did not decrease the level of killing. The inherent resistance of F62 in these tests was probably due to LPS sialylation by CMP-NANA and lactate present in the phagocytes. A JB1 variant expressing the invasion-associated Opa protein was as able to enter Chang human conjunctiva epithelial cells as an Opa-positive variant of F62, suggesting that the sialyltransferase is not required for Opa-mediated entry. After incubation with CMP-NANA, the number of F62 variant gonococci entering cells but not that of JB1 variant gonococci was drastically reduced. Both JB1 and F62 were killed by incubation with rabbit antibody to gonococcal major outer membrane protein, protein I, and human complement, but only F62 was rendered resistant to the killing by incubation with CMP-NANA. Finally, both JB1 and F62 absorbed similar amounts of complement component C3 and the binding was decreased by incubation with CMP-NANA only for the wild type, F62.
 ...
PMID:Functional characterization of a sialyltransferase-deficient mutant of Neisseria gonorrhoeae. 875 78

The heavy- and light-chain variable regions from a murine monoclonal antibody that recognize Pseudomonas aeruginosa serogroup O6 lipopolysaccharide (LPS) were used to generate a series of chimeric mouse-human monoclonal antibodies with identical variable regions. The murine variable-region gene segments were cloned into an immunoglobulin (Ig) cDNA expression vector that contained the human kappa light-chain and IgG1 constant regions. The IgG1 heavy-chain constant region was then replaced with the human IgG2, IgG3, IgG4, or IgA1 heavy-chain constant region. The five different expression vectors were transfected into Chinese hamster ovary cells for antibody production. The chimeric antibodies exhibited immunoreactivity and affinity similar to that of the parental murine IgG antibody toward whole cells of a serogroup O6 strain. In vitro complement deposition assays demonstrated that the chimeric IgG4 and IgA antibodies did not mediate the deposition of complement component C3 onto the surface of either purified LPS or whole bacteria. The chimeric IgG1 and IgG3 antibodies were similar in their ability to deposit C3 onto the surface of both bacteria and LPS, while IgG2 antibody was more effective at depositing C3 onto the surface of bacteria than onto purified LPS. The pattern of opsonophagocytic activity of the chimeric monoclonal antibodies was similar to that of complement deposition onto bacterial cells in that the chimeric IgG1 and IgG3 had the highest opsonic activity. Although IgG2 deposited more C3 onto the bacterial surface than did IgG4 or IgA, all three of these isotypes had low opsonic activity against the serogroup O6 target strain. This series of related antibodies will help reveal functional differences in efficacy among protective antibodies to P. aeruginosa and will be critical for defining the optimal formulation of either a vaccine for active immunization or a polyclonal intravenous IgG or monoclonal antibody cocktail for passive immunotherapy.
 ...
PMID:Production and characterization of a set of mouse-human chimeric immunoglobulin G (IgG) subclass and IgA monoclonal antibodies with identical variable regions specific for Pseudomonas aeruginosa serogroup O6 lipopolysaccharide. 971 59

The effect of endotoxemia and sepsis on mucosal production of the acute-phase proteins complement component C3 and serum amyloid A (SAA) was studied in mice. In addition, the role of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)(-1)beta, and IL-6 on mucosal C3 and SAA production was examined. Endotoxemia was induced by the subcutaneous injection of 250 microg/mouse of lipopolysaccharide. Control mice were injected with corresponding volumes of sterile saline solution. Sepsis was induced by cecal ligation and puncture, and sham-operated mice served as controls. Endotoxemia resulted in increased mucosal C3 levels in all parts of the gastrointestinal tract examined, from the stomach to the colon, with the most pronounced effects noticed in the proximal gastrointestinal tract. The influence of endotoxemia on mucosal SAA production was more differentiated with increased levels noted in the jejunum and ileum, and no changes seen in gastric and colonic mucosa. Sepsis resulted in similar changes in mucosal C3 and SAA levels as seen in endotoxemic mice, except that SAA levels were increased in colonic mucosa of septic mice. Among the cytokines, IL(-1)beta resulted in the most pronounced changes in mucosal acute-phase proteins. The increase in C3 and SAA levels in the mucosa of the small intestine during endotoxemia was partially blocked by IL(-1) receptor antagonist. The results suggest that endotoxemia is associated with increased mucosal C3 production in different parts of the gastrointestinal tract and increased SAA production in the mucosa of the small intestine. Mucosal acute-phase protein synthesis may, at least in part, be regulated by IL(-1)beta.
 ...
PMID:Mucosal production of complement C3 and serum amyloid A is differentially regulated in different parts of the gastrointestinal tract during endotoxemia in mice. 1045 12

We have previously demonstrated the existence of Klebsiella pneumoniae clinical isolates deficient in the lipopolysaccharide O side chain, the major factor for resistance to complement-mediated killing in this bacterial species. These isolates are complement resistant, and their mechanisms to resist complement were investigated by selecting transposon-generated complement-sensitive mutants. One mutant with a drastically reduced capacity to grow in nonimmune human serum carried the transposon inserted in an open reading frame of a gene cluster involved in capsule synthesis. This mutant produced less capsule, bound more molecules of the complement component C3, and was more sensitive to complement-mediated and opsonophagocytic killings than was the parent strain. Four additional clinical isolates representing four different K serotypes were studied, and results showed that capsular polysaccharide is a major complement resistance factor in these O side chain-deficient isolates.
 ...
PMID:Capsular polysaccharide is a major complement resistance factor in lipopolysaccharide O side chain-deficient Klebsiella pneumoniae clinical isolates. 1063 70


1 2 3 Next >>