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)

To investigate whether the formation of IgE is linked in vivo to an IgG subclass, mice were infected with four helminth parasites, Nippostrongylus brasiliensis (Nbr), Mesocestoides corti, Taenia crassiceps and Trichinella spiralis, and the changes in the serum levels of the different Ig isotypes as well as the antibody response to M. corti and T. crassiceps antigen extracts were determined by radioimmunoassays. All four parasites induced a concomitant increase of the IgE and IgG1 serum levels and usually a decrease of the IgG2a level. They also induced an increase of the IgM level but had little effect on the IgG2b, IgG3, and IgA serum levels. The specific antibodies to an M. corti antigen extract were mainly of the IgG1 subclass, whereas it was of both IgG1 and IgG2a subclasses to T. crassiceps. Injections of dead M. corti induced an increase of all IgG subclasses and similar levels of IgG1 and IgG2a anti-parasite antibodies. Subcutaneous instead of intraperitoneal infection with T. crassiceps induced higher IgG2a than IgG1 levels and 10-fold lower IgE levels than the natural ip infection; however, despite the greater IgG2a polyclonal response, anti-parasite antibodies were predominantly of the IgG1 subclass. The data demonstrate that natural infection with four different helminth parasites induces a concomitant polyclonal IgG1 and IgE response. These in vivo observations corroborate the recent in vitro findings demonstrating that interleukin-4 induces lipopolysaccharide-activated murine B cells to secrete both IgG1 and IgE, suggesting that the regulation of these two isotypes is linked.
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PMID:The IgE and IgG subclass responses of mice to four helminth parasites. 252 26

The cDNA encoding the murine low-affinity receptor for IgE (Fc epsilon RII) has been isolated from a cDNA library prepared from B cells activated with lipopolysaccharide and interleukin 4. It encodes a 37-kDa protein of 331 amino acids with two potential N-linked glycosylation sites. Analogous to its human counterpart, there is no signal sequence and the putative transmembrane region is close to the amino terminus, indicating an inverse membrane orientation with the carboxyl terminus at the cell exterior. The predicted murine Fc epsilon RII amino acid sequence demonstrates a 57% identity with its human counterpart. The murine sequence has an additional internal repeat motif of 21 amino acids giving four repeats as compared to three in the human sequence. Furthermore, the murine Fc epsilon RII is truncated at the carboxyl terminus and the Arg-Gly-Asp sequence, a common recognition site of integrin receptors, which is found in the reverse configuration in human Fc epsilon RII, is missing. B cells activated with interleukin 4 and lipopolysaccharide have an increased amount of Fc epsilon RII mRNA as compared with resting or lipopolysaccharide-stimulated B cells. Con A-activated normal T cells, the TH-2 cell line D10, as well as the macrophage cell line J774 have no detectable Fc epsilon RII mRNA. Expression analysis using transiently transfected COS cells revealed that recombinant murine Fc epsilon RII binds anti-Fc epsilon RII as well as mouse and rat IgE but does not bind human IgE or mouse IgG. Fc epsilon RII expressed in COS cells has a molecular mass of 45 kDa whereas the Fc epsilon RII from B-cell lines is a 49-kDa protein.
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PMID:Molecular structure and expression of the murine lymphocyte low-affinity receptor for IgE (Fc epsilon RII). 252 42

The cytokine interleukin 4 (IL-4) has been shown to induce lipopolysaccharide-activated murine B cells to differentiate into IgE-secreting cells and to stimulate IgE secretion by cultured human peripheral blood lymphoid cells. It is unclear, however, whether this effect of IL-4 on human peripheral blood lymphoid cells is a direct effect on the B cell because IL-4 can stimulate T cells and monocytes as well as B cells and does not induce purified human B cells to secrete immunoglobulin. To investigate this issue we studied the ability of IL-4 to induce IgE secretion by purified human B cells (93-96% CD20+, less than 1% CD3+) that were cultured with Epstein-Barr virus (EBV). Although B cells cultured with IL-4 alone did not secrete Ig and B cells cultured with EBV alone secreted IgM, IgG, and IgA but less than 150 pg of IgE per ml, the combination of EBV and IL-4 induced an IgE response that ranged from 11.4 to 40.3 ng/ml of culture supernatant after 26 days of culture. While IL-4 also enhanced IgM, IgG, and IgA secretion, as well as proliferation by EBV-infected B cells, these effects were less pronounced, occurred earlier during culture, and required a lower concentration of IL-4 than did the stimulation of IgE secretion. Furthermore, interferon gamma at 10 units per ml was found to inhibit IL-4/EBV-induced IgE secretion without inhibiting the other stimulatory effects of IL-4. We conclude that (i) IL-4 and interferon gamma can act directly on polyclonally activated human B cells to respectively stimulate and suppress IgE secretion and (ii) IL-4, in addition to its specific effect on IgE secretion, has a general stimulatory effect on the growth and differentiation of EBV-infected human B cells.
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PMID:IgE secretion by Epstein-Barr virus-infected purified human B lymphocytes is stimulated by interleukin 4 and suppressed by interferon gamma. 254 58

Preincubation of human basophils with bacterial lipopolysaccharide (LPS) purified from the heptose-deficient mutant Salmonella minnesota R595 enhanced by an average of sixfold the response of peripheral blood basophils obtained from allergic donors to several allergens in vitro as judged by release of histamine. Enhancement occurred at suboptimal, optimal, and supraoptimal concentrations of antigen. No effect was seen if basophils were from a nonallergic donor, and LPS by itself rarely caused histamine release from any preparation of basophils. However, histamine release in basophils from nonallergic donors induced by antibody directed against IgE (anti-IgE) also was enhanced by LPS. Potentiation of histamine release occurred if basophils were pretreated with LPS before addition of anti-IgE for as little as 5 min; there was no increase in release if anti-IgE and LPS were added simultaneously to cells. LPS enhanced the rate of release without altering duration of the release response. LPS potentiation of release of histamine by F(ab')2 fragments of anti-IgE was equivalent to its effect on release triggered by the intact antibody molecule, confirming that the effect of LPS is not due solely to its interaction with the Fc component of the anti-IgE. These data thus provide evidence for modulation of basophil response to IgE-mediated stimuli by LPS, resulting in a significant enhancement of response. Enhancement by LPS appears to be independent of the stimulus which triggers the IgE receptor. The contribution of this mechanism to allergic disease or asthma remains to be determined.
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PMID:The effect of bacterial lipopolysaccharide (LPS) on histamine release from human basophils. I. Enhancement of immunologic release by LPS. 257 9

The murine B cell lymphoma I.29 contains cells expressing surface IgM or IgA with identical heavy chain variable regions (9, 25, and D. Klein and J. Stavnezer, unpublished data). Purified IgM+ cells from the lymphoma have been adapted to culture and induced to switch to IgA, IgE, or IgG2 by treatment with lipopolysaccharide (LPS) or by treatment with a monoclonal anti-I.29 antiidiotype plus LPS. Clones of IgM+ cells have been obtained and induced to switch. Under optimal conditions, 30% of the cells in the culture expressed IgA 8 d after the inducers were added, and by 15 d 90% of the cells were IgA+. In actively switching cultures, up to 50% of the cells whose cytoplasm stained positively with anti-IgA stained simultaneously with anti-IgM, which indicates that the appearance of IgA+ cells in the cultures was due to isotype switching and not to clonal outgrowth. Examination by Southern blotting experiments of the Ig heavy chain genes in I.29 cells before and after switching revealed that isotype switching was accompanied by DNA recombinations that occurred within or immediately 5' to the tandemly repeated switch sequences. Within 3 d after the addition of inducers of switching, the nonexpressed chromosome underwent a variety of deletions or expansions within the S mu region, and a portion of the S alpha regions had undergone a 0.9-kb deletion. In cultures that contained at least 12% IgA+ cells, rearranged, expressed alpha genes, produced by recombination between the S mu region within the expressed mu gene and the S alpha region, were detected.
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PMID:Induction of immunoglobulin isotype switching in cultured I.29 B lymphoma cells. Characterization of the accompanying rearrangements of heavy chain genes. 257 86

Immunoglobulin (Ig) production by lipopolysaccharide (LPS)-stimulated cells in the presence of various combinations of interleukin (IL)2, IL4 and IL5 was examined. IgG1, IgM and IgE secretion was studied using a 3T3-fibroblast filler cell-supported B cell culture system, either at low cell density to support maximal Ig secretion, or at limiting dilution to determine isotype-specific precursor frequencies. In the presence of optimal concentrations of IL5 (2%) and IL2 (3 U/ml), the addition of 1 U/ml of IL4 resulted in the production of 4 ng of IgG1 per input B cell. In contrast, 1000 U/ml of IL4 alone was required to produce equivalent levels of IgG1. IL5 and IL2 increased both the precursor frequency and the amount of IgG1 secreted per clone in the presence of low levels of IL4. On the other hand, IgM secretion was decreased 10-fold by the addition of 10 U/ml IL4 or greater. This was not seen when IL5 was present. The IgM-secreting precursor frequency was unaffected by any of the lymphokines, either singly or in combination. The inhibition of IgM production and subsequent relief of this with IL5 was shown to affect the amount of IgM secreted per clone. IgE secretion was shown to be highly IL4 dependent with only minor reduction in the required concentration following addition of IL5 and IL2. At the clonal level, the majority of IgE-secreting clones (93%) at high IL4 concentrations (200 U/ml) arose from precursors which were able to produce IgM and IgG1. Furthermore, only 3% of the clones secreted IgG1 alone, with a further 3% secreting IgE alone. These results suggest that B cells in vivo are predominantly uncommitted in terms of isotype to be produced, the choice of isotype secreted being dependent on the nature of the stimulus. Overall, this work shows that the isotype secreted by B cells can be regulated using combinations of IL2, IL4 and IL5, and that major effects can be achieved by very small quantities of lymphokines acting in synergy.
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PMID:Combinations of interleukins 2, 4 and 5 regulate the secretion of murine immunoglobulin isotypes. 259

Regulation of a memory IgE antibody response may be different from the induction of a primary response and may, therefore, be more relevant to the study of allergic diseases and the therapeutic manipulation of IgE antibody formation. In this paper a murine hapten-specific in vitro memory IgE antibody response to benzylpenicilloyl(BPO)-KLH is described. The response was analyzed by determining the number of antibody-producing cells (APC) in an ELISA spot assay. Of the total number of BPO-specific APC (10,000 APC/10(6) cultured spleen cells), about 1% were IgE-producing cells (100/10(6) cultured cells), as detected on day 6 of culture. The level of the antibody response is antigen dose-dependent, and the detected APC are BPO specific. The memory IgE response is not inhibited by the addition of anti-IL-4 antibody (11B11), even at a high excess. In the presence of the mitogen lipopolysaccharide, it has been shown that switch of B cells to IgE is induced by IL-4, a process which can be inhibited by anti-IL-4 antibody. Because the antigen-induced IgE response cannot be inhibited by anti-IL-4 antibody, in vitro responding cells derived from BPO-KLH-preimmunized mice may, therefore, have already switched in vivo to IgE. On the other hand, B cells switching to IgE in a situation of cognate T-B cell interaction might receive IL-4 in a transsynaptical way from T cells which might not be accessible to inhibition by anti-IL-4 antibody. The identification of the two possibilities in situations of established allergic disorders will be decisive for determining whether pharmacological inhibition of IL-4 (or IL-4-induced switch)--e.g., by putative low molecular weight compounds--will ever be a meaningful approach to suppress allergic diseases.
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PMID:Establishment of a memory in vitro murine IgE response to benzylpenicillin and its resistance to suppression by anti-IL-4 antibody. 261 52

Sequential sublining was used in combination with enzyme-linked immunosorbent assays to isolate mu----gamma isotype switch variants of the rat IgM secreting mouse-rat B cell hybridoma line BA1.8. Switch variants to all four subclasses of IgG were obtained. The variant antibodies retained the antigen specificity of the parental IgM for the O18 (lipopolysaccharide) antigen of Escherichia coli. In sodium dodecyl sulfate-polyacrylamide gels the apparent molecular mass of the gamma heavy chains decreased in the order gamma 2b greater than gamma 1 greater than gamma 2c greater than gamma 2a. IgM, IgG1, IgG2a, IgG2b and IgG2c of the BA1.8 variant family and IgG2b, IgE and IgA of the previously described BA1.2 family were used for a comparative analysis of the capacity of rat Ig to activate complement. Efficient lysis of sheep erythrocytes coated with the O18 antigen was observed with IgM and all IgG subclasses, but no lysis was triggered by IgE or IgA. One hundred to 1000 IgG molecules were required to mediate the same hemolytic activity as one IgM molecule. The four IgG subclasses were equally efficient at mediating lysis by rat or human complement, while IgG2a was less efficient with guinea pig complement than the other three IgG subclasses. Antibody-triggered binding of C3 to pathogenic O18:K1 E. coli bacteria was measured using serum containing 125I-labeled C3. K1-encapsulated strains did not fix C3 efficiently in the absence of specific antibodies while acapsular mutants fixed C3 via the alternative pathway. IgM and all IgG subclasses triggered C3 binding to the K1 encapsulated bacteria. The capacity of IgM to mediate C3 fixation was not greater than that observed with IgG.
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PMID:Isolation of rat IgM to IgG hybridoma isotype switch variants and analysis of the efficiency of rat Ig in complement activation. 264 34

A rapid, specific and sensitive radiometric assay was developed capable of quantitating serum levels of HA-1A, a human IgM monoclonal antibody to endotoxin. 'Private' anti-idiotypic murine monoclonal antibodies were produced and utilized in the assay to avoid cross-reactivity with normal human IgG, IgM, IgA, IgE or IgD. The presence of E. coli or gram-negative lipopolysaccharide in the sera did not affect the ability of the assay to detect HA-1A. The sensitivity of the assay was calculated to be 25 ng/ml with an interassay coefficient of variation of less than 10%. In one patient given 100 mg of HA-1A, peak serum concentration was 101.5% of the predicted value with a mean plasma half life of 24.5 h. This assay will be useful in establishing the pharmacokinetics of HA-1A and in monitoring serum levels during phase II and phase III clinical trials.
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PMID:Quantitative assay of a human monoclonal IgM antibody (HA-1A) in human serum. 264 78

The effect of the castor bean toxin, ricin, on rat spleen and mesenteric lymph node cell cultures was tested. Rat lymphocytes were cultured for 2 days in the presence of optimal doses of the mitogens phytohaemagglutinin, conconavalin A, and lipopolysaccharide. At concentrations of 10(-3) to 10(-5) mg/ml ricin, spontaneous and mitogen-driven proliferation were inhibited. At lower concentrations, spleen but not mesenteric lymph node cells showed enhanced proliferation. Studies are continuing to identify subpopulations of lymphocytes with increased or decreased sensitivity to ricin and their role in the regulation of IgE.
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PMID:Effect of ricin on the proliferation of rat spleen and mesenteric lymph node cells. 270 86


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