Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A structural analysis of cells that contained the interferon-alpha-induced lupus inclusions (LI) was performed using a high-voltage electron microscope to determine the exact cellular location of LI and their association with normal cell organelles. LI were induced in the human B lymphoblastoid cell line, Daudi, by culturing with the pure recombinant human leukocyte interferon, IFLrA. Just prior to harvesting, a portion of the cells was treated with monensin to selectively swell the Golgi apparatus, and thereby simplify their identification using the electron microscope. Organellar associations between LI and the outer nuclear envelope and Golgi apparatus were identified in stereopairs of 1-micron sections prepared from both cells that were not treated with monensin and those that were treated with monensin. Serial 0.25-micron sections of the monensin-treated cells were prepared, and seven arbitrarily chosen cells were examined. Each of these cells contained a single LI, and it formed throughout an endoplasmic-reticulum region that made contact with both the outer nuclear envelope and the Golgi vesicles. Reconstruction of a cell by computer from the digitized negatives of serial sections clearly illustrated these relationships. This study reports the first determination of the association between LI and the Golgi apparatus. It also identifies the presence of only one LI in every cell, and the routine association of the LI with both the outer nuclear envelope and the Golgi apparatus. The unique cell location of LI formation suggests their functioning in membrane biogenesis, the trafficking of proteins to the plasma membrane or to cytoplasmic vesicles, or the processing of proteins for secretion.
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PMID:Localization of interferon-induced lupus inclusions demonstrated by computer image reconstruction of monensin-treated Daudi cells. 137 90

No differences in proliferation induced by the anti-CD3 MAb 454 were detected between systemic lupus erythematosus (SLE) and normal peripheral blood mononuclear cells (PBMC) or purified T cells. In contrast, overnight culture with soluble MAb 454, immobilized MAb 454, or rIL2 induced significantly less increase in cytolytic activity against Daudi targets in SLE PBMC than in normal PBMC. Cytolytic activity in SLE PBMC cultures sequentially stimulated with soluble MAb 454 and rIL2 over a 6-day period overall was also lower than normal (with approximately 50% of the individual SLE cultures generating clearly subnormal levels of cytolytic activity) and did not correlate with the daily corticosteroid dose or with the presence of nephritis. Phenotypic analysis of soluble MAb 454-stimulated SLE PBMC cultures maintained for up to 23 days in rIL2 indicated that greater than 90% (and often greater than 96%) of the recovered cells were CD3+. Cytolytic activity generated in cultures of purified T cells stimulated with soluble MAb 454 + rIL2 over a 6-day period was also subnormal in 4/8 SLE donors, suggesting that the impaired generation of cytolytic activity in SLE is caused, at least in part, by impaired T cell-mediated cytolytic activity. Taken together, these observations demonstrate that normal CD3/T cell antigen receptor (TCR)-triggered polyclonal T cell proliferation can be dissociated from abnormal CD3/TCR-triggered polyclonal T cell cytolytic activity in SLE. This may have important implications for the pathogenesis of SLE and/or for the immunocompromised state seen in SLE.
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PMID:Impaired generation of polyclonal T cell-mediated cytolytic activity despite normal polyclonal T cell proliferation in systemic lupus erythematosus. 161 18

Quantitative electron microscope autoradiography has been used to define the macromolecular composition of the interferon-induced human lupus-type inclusions (LI) in the human B lymphoblastoid cell line, Daudi. LI were first apparent in Daudi cell cultures 12 h after the addition of 100 units/ml of the purified recombinant human leukocyte interferon, IFLrA. Radiolabels were added at this time and allowed to incorporate over the following 12 h during which an estimated greater than 99% of the LI material present at 24 h was formed. The LI-incorporated radiolabels were present only during this discrete 12-h period after the interferon activation of LI cell pathways in order to detect LIs de novo synthesized macromolecular components. The estimate relative specific activities of the LI-incorporated radiolabels were: choline at 4.042, mannose at 2.631, uridine at 0.664, glucosamine at 0.578, and amino acids at 0.477. With thymidine the estimated LI specific activity was 0.000. LI isolated from whole cells retained the tubular elements and the interwoven membrane network. These results provide direct evidence that the interferon-induced Daudi cell LI are de novo synthesized complexes of ribonucleoprotein and membrane.
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PMID:Evidence that the interferon-induced Daudi cell human lupus inclusions are de novo synthesized complexes of ribonucleoprotein and membrane. 278 94

Human alpha interferons (IFN-a) cause a reorganization of internal cell membranes into tubuloreticular inclusions (TRI). Morphogenesis and cytochemistry indicate a pre-Golgi intracisternal origin from the endoplasmic reticulum. Clinically, TRI formation in human blood mononuclear cells correlates with systemic IFN-a treatment or with endogenous overproduction of IFN-a in viral or autoimmune diseases (e.g., rubella syndrome, AIDS, systemic lupus erythematosus). In vitro, TRI formation can be produced by treatment of Daudi lymphoblasts or vascular endothelial cells with IFN-a, and is blocked by actinomycin-D. In Daudi lymphoblasts or vascular endothelial cell cultures, TRI formation parallels induction of 2'-5' A synthetase, inhibition of thymidine kinase and growth inhibition; however, heavy water treatment of Daudi cells prevented TRI formation while induction of 2'-5' A synthetase and growth inhibition persisted. TRI formation was dissociated from IFN-a antiproliferative activity in a mutant clone of Daudi lymphoblasts. Decreased glycoprotein biosynthesis and increased phospholipid biosynthesis may accompany progressive TRI accumulation.
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PMID:Tubuloreticular reorganization of cytomembranes in cells treated with human alpha interferons--a review. 307 Jul 35

A sensitive in vitro bioassay for the alpha-interferon induction of lupus-type inclusions (LI) has been established with the human B lymphoblastoid cell line, Daudi. Sera from 11 patients with systemic lupus erythematosus (SLE) were evaluated with this assay. LI induction by these sera increased in proportion to their antiviral activity on Madin-Darby bovine kidney (MDBK) cells. Two of these sera did not induce LI; they showed no antiviral activity on the MDBK cell assay. Clinically and serologically, their donors were in remission. Two sera induced the formation of LI that exceeded the maximum frequencies obtained with 3 alpha-interferon preparations. These sera had the greatest antiviral activities, and their donors had the greatest disease activities. Antisera to alpha-interferons prevented the induction of LI with the pure and homogeneous recombinant human leukocyte interferon, IFLrA, and SLE sera. Together, these results provide evidence that the alpha-interferon endogenous to SLE patients has a great ability to induce LI, and the SLE serum induction of LI corresponds well to the patient's disease activity.
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PMID:Induction of lupus inclusions by sera from patients with systemic lupus erythematosus. 348 63

Raji and Daudi are human B lymphoblastoid cell lines that readily form lupus inclusions (LIs; TRS) when grown in medium supplemented with leukocyte-, or fibroblast-derived interferon (IFN-alpha, -beta, respectively). WISH, MDBK, and GM2504 are three cell lines commonly used to measure antiviral activities. None of them form LIs in their antiviral response to alpha or immune (gamma)IFN. This distinguishes between the abilities of a cell to develop an antiviral state and to form LIs in response to IFN. Human (Hu) lymphoblastoid IFN and the two pure and homogeneous recombinant human IFN-alpha proteins IFLrA and IFLrD induce LIs in Raji cells and Daudi cells. In Daudi, a simultaneous inhibition of cell growth occurs. When compared by antiviral activities, IFLrA inhibits the growth of Daudi cells more, while IFLrD induces the greater frequency of LIs. According to molecular concentration, IFLrA and IFLrD at 133 X 10(-13) M induce LIs in Daudi cells to their maximum frequency. Growth inhibition for these same cell samples is also at maximum for IFLrA, but only 25% of maximum for IFLrD. Our results with Raji and Daudi cells provide evidence against a cause-and-effect relationship between these two biologic responses to IFN by Daudi cells. They also provide evidence for distinct, but interacting, intracellular pathways. This phenomenon is a new explanation for some of the biologic diversity shown for the HuIFNs-alpha.
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PMID:Purified recombinant human leukocyte interferons IFLrA and IFLrD induce human lupus inclusions in Raji and Daudi cells. 609 90

The human IFI 16 gene encodes a nuclear protein whose expression is associated with activation and differentiation of cells of the myeloid lineage, and which has recently been postulated to be a frequent target of human autoantibodies. We have used a unique monoclonal antibody in immunofluorescence studies to define the intranuclear distribution of IFI 16 antigen in primary human leukocyte sub-populations. We demonstrate that IFI 16 is expressed both within the nucleoli and nucleoplasm of mononuclear cells, but is not present in granulocytes. IFI 16 expression correlated with that of the known nucleolar antigen B23, suggesting that the function of IFI 16 is restricted to cells that have nucleoli and therefore are not terminally differentiated. These findings were supported by immunofluorescence studies in IFN-gamma-stimulated HL-60 cells and by biochemical fractionation of Daudi nuclear extract. IFI 16 was extracted from whole nuclei at approximately 200-300 mM NaCl, within the range described for known transcription factors. Together with our previous findings, these results support a possible role of IFI 16 in binding nucleic acid in vivo. Furthermore, a DNA-binding site was localized within a fusion protein containing the amino-terminal 159 amino acids. As the nucleic acid-binding domains of several proteins are targeted by autoantibodies in SLE, this region may be of significance in the pathogenesis of autoimmune disease.
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PMID:The interferon-inducible autoantigen, IFI 16: localization to the nucleolus and identification of a DNA-binding domain. 754 91

In response to the pure recombinant human alpha-IFN, IFLrA, Raji and Daudi were the only two cell lines among 19 human lymphoblastoid cell lines tested that formed the human lupus inclusions (LI) to a high frequency. Raji, Daudi, and five other cell lines were examined for protein changes that might accompany LI formation. Their selection was based upon T or B origin, association with Epstein-Barr virus, and ability to form LI. A trace protein of an estimated molecular mass of 36 kD (p36) and an isoelectric point of 5.6 was detected on two-dimensional gels only of alpha-IFN-treated Raji and Daudi cells. Gamma-IFN did not induce p36 or LI in any of these seven cell lines. In Daudi cells p36 and LI formed simultaneously in response to IFLrA, and persisted until the alpha-IFN-induced death of the culture. In Raji cells, p36 and LI appearance and disappearance coincided with the addition and removal of alpha-IFN. Fractionation of Raji cells with nonionic-detergent buffer placed p36 with the inclusions in the cytoplasmic supernatant. With detergent-free buffer p36 and LI were distributed evenly between the nuclear and cytoplasmic fractions. Pulse-chase experiments revealed that p36 was secreted. The de novo synthesis of p36 with alpha-IFN treatment was shown by labeling the cell proteins with [35S] methionine before and after the addition of alpha-IFN. These results along with previous results on the de novo synthesis of LI in the endoplasmic reticulum (which is involved in the processing and secretion of proteins) suggest a role for LI in the synthesis and secretion of p36.
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PMID:De novo synthesis and secretion of a 36-kD protein by cells that form lupus inclusions in response to alpha-interferon. 781 19

Western blotting with U937 cell extracts as the substrate, and enzyme-linked immunosorbent assays (ELISA) with U937-, Jurkat- and Daudi cell-purified CD45 molecules were used to detect anti-CD45 reactivity in patients with systemic lupus erythematosus (SLE). By immunoblotting, 16 of 64 SLE sera were shown to be positive (25.0%). In the ELISAs, 13 out of 18 SLE sera reacted with the target CD45. Of these, three were not detectable on the blot. Importantly, 12 of these ELISA-positive sera contained IgM and IgG auto-antibodies. Neuraminidase-treatment of U937-precipitated CD45 molecules enhanced the reactivity to most of the isoforms, indicating that the antibodies may bind to asialylated polysaccharides.
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PMID:Autoantibodies to CD45 in systemic lupus erythematosus. 980 33

The cell surface protein tyrosine phosphatase CD45 is a major target of IgM anti-T cell autoantibodies in systemic lupus erythematosus (SLE). The autoreactive determinants on CD45 are O-linked glycans expressed on activated T cells and certain T cell lines, rather than linear or conformational polypeptide epitopes or N-linked glycans. To identify oligosaccharide structures that may play a role in the functional interactions of CD45 or are candidate target epitopes of SLE anti-CD45 autoantibodies, autoreactive CD45 purified from Jurkat T cells and non-autoreactive CD45 purified from CLL B cells were tested by ELISA for expression of mucin-type O-glycan structures. Monoclonal antibodies (mAbs) directed against blood group A, type 1 H chains, type 2 H chains, T, Le(a), sialylated-Le(a), Le(b), sialylated-Le(c), Le(x), sialylated-Le(x), multi-fucosylated Le(x), Le(y), and sialylated-extended Le(v) failed to react with CD45 from either B cells or T cells. However, mAbs directed against Tn (galNAcalpha1-->O-ser/thr) or sialosyl-Tn (neuNAcalpha2-6gaINAcalpha1-->O-ser/thr) structures reacted with CD45 derived from Jurkat T cells, but not from CLL B cells. Anti-Tn mAbs also reacted in western blotting procedures with CD45 isolated from Jurkat T cells, but did not react with CD45 isolated from CEM, MOLT-3, or PEER T cells; Daudi, Raji, or CLL B cells; or resting or Con A-activated PBL. However, anti-sialosyl-Tn mAbs stained blots of CD45 isolated from Jurkat and CEM T cells and Con A-activated PBL, a pattern of reactivity similar to that of the anti-CD45 autoantibodies. Flow cytometric analyses demonstrated that the sialosyl-Tn epitopes are expressed on a subpopulation of CD4 +/CD8- T cells.
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PMID:Expression of the sialosyl-Tn epitope on CD45 derived from activated peripheral blood T cells. 984 19


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