SummaryIn comparison with HLA-A and -B, the protein products of the HLA-C locus are poorly characterized, in part because of their low level of expression at the cell surface. Here, we examine how protein-protein interactions during assembly and regulation of the mRNA level affect cell surface expression of HLA-C. We find that intrinsic properties of the HLA-C heavy chain proteins do not correlate with low cell surface expression: HLA-C heavy chains associate and dissociate with fl2-microglobulin (fl2m) at rates comparable to those found for HLA-A and -B, and increased competition for fl2m does not alter the surface expression of HLA-C. From studies of chimeric genes spliced from the HLA-B7 and -Cw3 genes, we find that chimeric proteins containing the B7 peptide-binding groove can have low cell surface expression, suggesting that inefficiency in binding peptides is not the cause of low cell surface expression for HLA-C. The surface levels of HLA-A, -B, or -C in cells transfected with cDNA can be similar, implicating noncoding regions of HLA-C heavy chain genes in the regulation of surface expression. We find that HLA-C mRNA is expressed at lower levels than HLA-B mRNA and that this difference results from faster degradation of the HLA-C message. Experiments examining chimeric B7/Cw3 and B7/Cw6 genes suggest that a region determining low expression of HLA-C is to be found between the 3' end of exon 3 and a site in the 3' untranslated region, '~600 bases downstream of the translation stop codon.
SUMMARYUsing an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% ± 52 8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% ±35-9). Seventy normal human sera had a mean BI of 10% ±9 8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (/'<0 001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0-68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role ofthese antibodies as a marker in lupus nephritis is discussed.
In this report, the mechanism through which interferon-gamma (IFN-gamma) regulates the expression of nitric oxide synthase (NOS-1) in neurons was examined. We have shown previously that IFN-gamma treatment of cells results in a two log inhibition of vesicular stomatitis virus (VSV) production. This inhibition of VSV replication is dependent both in vitro and in vivo on nitric oxide (NO) production by NOS-1. Furthermore, this effect is associated with the increased expression and activity of NOS-1 following IFN-gamma treatment. In vitro, exposure to IFN-gamma prior to infection with VSV is a prerequisite to establish an effective antiviral state, indicating the necessity for a priming event. Neuroblastoma cells (NB41A3) were treated with IFN-gamma or medium and examined for changes in NOS-1 protein and mRNA expression. NOS-1 protein expression was found to be increased after IFN-gamma treatment, and this was associated with increases in both neosynthesis and NOS-1 protein stability. NOS-1 transcription and mRNA levels were unaffected by IFN-gamma treatment. These data demonstrate that IFN-gamma regulates NOS-1 expression through posttranscriptional and posttranslational mechanisms.
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