bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-1 induces expression of monocyte chemoattractant JE in clonal mouse osteoblastic cell line MC3T3-E1.
Authors: Takeshita A , Hanazawa S , Amano S , Matumoto T , Kitano S 
Published: December 2022

Abstract
Recent studies demonstrated that platelet-derived growth factor-inducible JE is an inflammatory cytokine that directs chemotaxis of monocytes, and is a homolog of monocyte chemoattractant protein-1, which is a human monocyte chemotactic factor. Migration and accumulation of monocyte lineage cells in bone tissue sites are very important for the recruitment of multinucleate osteoclasts, because the origin of osteoclasts is derived from monocyte lineage cells in hemopoietic cells. Because IL-1 is a potent regulator in bone remodeling, we examined whether IL-1 beta induces JE expression in a clonal mouse osteoblastic cell line, MC3T3-E1. Significant chemotactic activity for human monocytes was detected in conditioned medium of the cells at 6 h after initiation of IL-1 beta treatment, and the chemotactic activity increased in both a culture time- and dose-dependent manner. The peak of the chemotactic activity in the conditioned medium was observed in fractions corresponding to a m.w. of 26 kDa when the conditioned medium was fractionated by gel filtration. The chemotactic activity in the peak fraction was completely neutralized by antiserum specific for JE protein. And the JE gene product in the conditioned medium was detected as a microheterogeneous protein with a m.w. of 21 to 33 kDa by immunoprecipitation with the specific antiserum. IL-1 beta induced a maximal JE gene expression in the cells at 3 h after initiation of the cytokine treatment. This significant expression was observed when IL-1 beta was used at a concentration of 10 U/ml, and the expression was dose dependent. The run-on assay showed that the cytokine-induced JE gene expression increased at the transcriptional level. IL-1 beta and TNF-alpha acted synergistically to stimulate JE gene expression in the cells. Expression and product of the JE gene were also observed in an osteoblast-enriched cell population prepared from mouse calvariae. These results suggest the possibility that osteoblastic cells can participate in osteoclast recruitment via the JE gene product.
V region gene analysis of anti-Sm hybridomas from MRL/Mp-lpr/lpr mice.
Authors: Bloom D D , Davignon J L , Retter M W , Shlomchik M J , Pisetsky D S , Cohen P L , Eisenberg R A , Clarke S H 
Published: December 2022

Abstract
Anti-Sm autoantibodies are unique to SLE, but are present in only 25% of patients with this disease. This response also occurs at a similar frequency in mice of the autoimmune MRL strains. Previous analyses of the anti-Sm response in these mice indicate that its occurrence is controlled by stochastic events, and suggest that Sm is the driving Ag. To further elucidate the role of Ag in this response, and to test the hypothesis that the 25% incidence is due to a requirement for particular Ig gene rearrangements or somatic mutations, we have analyzed the specificity and V-region gene sequences of 41 anti-Sm B cell hybridomas derived from nine anti-Sm-positive MRL/Mp-lpr/lpr mice. The majority of hybridomas are specific for the D peptide of the Sm particle. Hybridomas of independent origin express unique VH/V kappa combinations with diverse junctional sequences and are variable in the extent of somatic mutation. Thus, the response does not appear to be dependent upon the occurrence of a rare Ig gene rearrangement or specific somatic mutation. The response exhibits restriction in JH and VH gene use, and in individual mice is oligoclonal, suggestive of Ag selection. In the few B cells for which mutations can be identified, the evidence for selection of mutant B lymphocytes, based on patterns of mutation, is ambiguous. However, there is remarkably little intraclonal diversity, suggesting that the overall mutation rates in these clones are low.
Specific modulation of T cells and murine experimental allergic encephalomyelitis by monoclonal anti-idiotypic antibodies.
Authors: Zhou S R , Whitaker J N 
Published: December 2022

Abstract
Acetylated peptide 1-9 from human myelin basic protein induces experimental allergic encephalomyelitis in PL/J mice through I-Au and TCR V beta 8.2. Murine mAb anti-Id directed against murine mAb to myelin basic protein peptide acetyl 1-9 was examined for effects on in vitro and in vivo T cell activities. Certain anti-Id, generated in PL/J mice, inhibited Ag-specific proliferation and IL-2 production and precipitated surface receptors having features of the TCR. The idiotypic features of TCR recognition were demonstrated by showing that binding of anti-Id to the TCR could be blocked by anti-TCR alpha beta and anti-TCR V beta 8.1-8.2 but not by murine Ig or anti-TCR V beta 17a. In addition, the anti-Id did not react with TCR V beta 8.2 transgenically inserted into MRL+/+ mice. One anti-Id was also capable of lessening clinical disease activity in the adoptive passive transfer model of experimental allergic encephalomyelitis in PL/J mice. These results indicate that anti-Id may recognize a cross-reactive Id on T cells, presumably on the TCR, responsive to the same I-Au-restricted encephalitogenic myelin basic protein peptide in PL/J mice. The selective development of anti-Id and their effect on T cell-mediated tissue damage provide a method for applying specific anti-Id antibodies to modify experimental and, possibly, spontaneous diseases of autoimmune demyelination.
Molecular mechanisms underlying lymphocyte recirculation. III. Characterization of the LECAM-1 (L-selectin)-dependent adhesion pathway in rats.
Authors: Tamatani T , Kuida K , Watanabe T , Koike S , Miyasaka M 
Published: December 2022

Abstract
LECAM-1 (L-selectin) is thought to play an important role in the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes (LN), which is an essential process in lymphocyte recirculation. Previously we cloned the rat LECAM-1 cDNA. In this study, by using this probe we have sought to characterize a LECAM-1-dependent adhesion pathway in the rat. We have constructed a cDNA for rat LECAM-1-IgG chimera (rLEC-IgG), expressed it, purified the secreted recombinant chimera molecules, and produced mAb reactive with the rat homologue of LECAM-1 by using the chimera molecules. The use of rLEC-IgG revealed that ligands for LECAM-1 are selectively accumulated in high endothelial (HE) cells in LN, the white matter, neurons, cerebellar Purkinje cells, and choroid plexus of the central nervous system and also distal tubules and capillary blood vessels of the kidney. Binding of lymphocytes to LN HEV on frozen sections was blocked by either rLEC-IgG or the anti-rat LECAM-1 mAb. An HEV-derived cell line, Ax, specifically bound to rLEC-IgG fixed on plastic plate. Consistent with the presence of a C-type lectin domain in the ligand-binding region of LECAM-1, the binding was Ca2+ dependent and inhibitable by either the mannose-6-phosphate-rich polysaccharide polyphosphomannan ester or the anti-rat LECAM-1 mAb. These results indicate that the specific ligand for rat LECAM-1 is expressed on the Ax cells. rLEC-IgG precipitated 55-, 65-, 120-, 190-, and &gt; 250-kDa sulfated glycoproteins from LN lysates and 190-, &gt; 250-, and &gt; 500-kDa proteins from Ax cell lysate. The precipitation was Ca2+ dependent and LECAM-1 specific. These results suggest that a carbohydrate structure on HE cells recognized by LECAM-1 is borne possibly on a limited number of cell surface-sulfated glycoproteins. The ligands were also found to be secreted in LN culture supernatants. rLEC-IgG and Ax cells should prove valuable for studying further the role of LECAM-1 in dynamic interactions between lymphocytes and HE cells.
TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins.
Authors: Lee G W , Lee T H , Vilcek J 
Published: December 2022

Abstract
TNF-stimulated gene (TSG)-14 was originally identified as a TNF-inducible gene in a differentially screened cDNA library derived from TNF-treated normal human FS-4 fibroblasts. Analysis of the TSG-14 cDNA sequence revealed a major open reading frame encoding a protein of 381 amino acids, including a hydrophobic signal peptide sequence. The predicted protein shows 23 to 27% sequence homology to C-reactive protein and serum amyloid P-component, members of the pentaxin family of acute phase proteins. In addition, TSG-14 protein contains a sequence motif common among the pentaxin proteins. The ability of the TSG-14 cDNA to encode a protein of the correct molecular size was confirmed in a cell-free transcription/translation system. In vitro translation in the presence of microsomes confirmed that the protein has a cleavable signal peptide sequence, and that it is glycosylated. TSG-14 mRNA is rapidly elevated from almost undetectable levels in untreated FS-4 cells to high levels in cells treated with TNF or IL-1. A moderate increase in TSG-14 mRNA was observed in FS-4 cells treated with the glucocorticoid dexamethasone. Nuclear run-on analysis indicated that TNF induces the expression of the TSG-14 gene at the transcriptional level, and that de novo protein synthesis is not required for induction of TSG-14 mRNA. Expression of TSG-14 mRNA was also detected after exposure to TNF in vascular endothelial cells; however, little or not expression of TSG-14 message was observed in cell lines derived from malignant tumors. Our data strongly suggest that TSG-14 is a novel member of the pentaxin family of acute phase proteins.
Conservation of binding site geometry among p-azophenylarsonate-specific antibodies.
Authors: Parhami-Seren B , Kussie P H , Strong R K , Margolies M N 
Published: December 2022

Abstract
Murine A/J anti-p-azophenylarsonate mAb that express a dominant cross-reactive Id are encoded by a single set of germ-line VH and VL region genes. The crystal structure of the Fab of antibody 36-71, which uses this canonical set of genes but is somatically mutated, was previously determined. An Fab 36-71:phenylarsonate complex was modeled, identifying amino acid side chains that were proposed as contact residues to hapten. The remarkable conservation of these residues among canonical anti-p-azophenylarsonate antibodies suggested that the overall binding site geometry was maintained among somatically mutated antiarsonate monoclonal antibodies. To test this hypothesis, we used the germ-line-encoded antibody 36-65 to construct mutant antibodies, using oligonucleotide-directed mutagenesis, which differed only at the putative H chain hapten-contacting residues, and measured their hapten binding. A framework residue at H chain position 47 involved in a hydrogen bond network with CDR residues was also mutated. Substitution of several amino acids at each position permitted evaluation of the stereochemical requirements for binding. The results indicate the importance of aromatic stacking of two H chain tyrosine residues against the phenyl ring of the hapten in maintaining affinity, as well as strict complementarity at H chain position 35. The results are consistent with the crystal model of the combining site, and provide further evidence for conservation of the three-dimensional binding site motif among antiarsonate antibodies that bear a dominant heritable ld.
Augmentation by IL-1 alpha of tumor necrosis factor-alpha cytotoxicity in cells transfected with adenovirus E1A.
Authors: Tsuji Y , Ninomiya-Tsuji J , Torti S V , Torti F M 
Published: December 2022

Abstract
The introduction of adenovirus E1A into NIH3T3 mouse fibroblasts renders them susceptible to the cytotoxic action of TNF-alpha. We found that cells transfected with 13S E1A cDNA were not similarly rendered sensitive to IL-1 alpha; however, in cells transfected with 13S E1A cDNA, TNF cytotoxicity was augmented by treatment with IL-1. To understand the role of E1A in the cytotoxic action of these cytokines, several 13S E1A cDNA deletion mutants were constructed, transfected into NIH3T3 cells, and tested for their ability to induce TNF sensitivity in the presence and absence of IL-1. Cells transfected with mutants of 13S E1A with deletions of carboxyl-terminal amino acids 223 to 289 or 151 to 289 (conserved region 3) exhibited a minimal ability to reverse E1A-induced TNF cytotoxicity but a significant ability to reverse IL-1-mediated augmentation of TNF cytotoxicity. Cells transfected with other deletion mutants of 13S E1A, including those with an internal deletion encompassing conserved region 1 (amino acid positions 23 to 107) or a deletion including conserved regions 2 and 3 (amino acid positions 108 to 289), although initially TNF resistant, became TNF sensitive on prolonged exposure to TNF. Cells transfected with these mutants also showed a reduction in IL-1-augmented TNF cytotoxicity. The larger internal deletion of E1A at amino acid positions 23 to 150 (conserved regions 1 and 2), which includes regions important for transformation, transcriptional repression, and association with cellular proteins, resulted in the complete loss of the ability of E1A to induce TNF sensitivity even in the presence of IL-1. Immunoprecipitation experiments showed that E1A proteins in NIH3T3 cells associated with a cellular 115-kDa protein, which did not co-migrate with the RB gene product; the possible involvement of this protein in E1A-mediated TNF cytotoxicity is discussed. Taken together, these results indicate that conserved regions 1 and 2 are required for E1A-mediated TNF cytotoxicity. In contrast, maximal IL-1-augmented TNF cytotoxicity requires conserved region 3 as well as the nonconserved carboxyl-terminal region of the 13S E1A product.
Cartilage degradation by cocultures of transformed macrophage and fibroblast cell lines. A model of metalloproteinase-mediated connective tissue degradation.
Authors: Janusz M J , Hare M 
Published: December 2022

Abstract
A number of human and mouse macrophage and fibroblast cell lines were examined for their ability to degrade cartilage proteoglycan in an attempt to establish a cell culture model of cartilage degradation. The mouse transformed macrophage cell line J774A.1 alone or in combination with the mouse transformed fibroblast cell line 10ME HD A.5R.1 were the only cell lines capable of extensively degradating cartilage proteoglycan. Incubation of the macrophage cell line J774A.1 on heat-killed cartilage disks resulted in the release of 36% +/- 8 (mean +/- SEM, n = 5) of the radiolabeled cartilage proteoglycan. The fibroblast cell line 10ME HD A.5R.1 alone did not degrade cartilage. However, cocultures of J774A.1 macrophages and 10ME HD A.5R.1 fibroblasts incubated on cartilage discs resulted in the release of 69% +/- 6 (mean +/- SEM, n = 5) of radiolabeled proteoglycan. There was little degradation of cartilage by macrophage/fibroblast cocultures during the first 3 days of culture. Cartilage degradation increased with each subsequent day in culture from 7% +/- 2 on day 4 to 68% +/- 3 (n = 3) by day 7. Supernatants from the macrophage/fibroblast cocultures were incubated with cartilage discs in the presence of general class-specific proteinase inhibitors. The metalloproteinase inhibitors 1,10 phenanthroline, EDTA, and recombinant tissue inhibitor of metalloproteinase were the only inhibitors that significantly blocked cartilage degradation by coculture supernatant. The cartilage degrading metalloproteinase in the macrophage/fibroblast coculture supernatant eluted as a broad peak on Sephacryl S-200HR with an estimated molecular mass between 22 and 55 kDa. These studies suggest that the macrophage/fibroblast coculture model of cartilage degradation may be a useful experimental system for the study of metalloproteinase-mediated connective tissue degradation.
Autoantibodies directed against different classes of Fc gamma R are found in sera of autoimmune patients.
Authors: Boros P , Muryoi T , Spiera H , Bona C , Unkeless J C 
Published: December 2022

Abstract
Serum samples from 147 patients with different systemic autoimmune diseases (SLE, Sjögren's syndrome, and progressive systemic sclerosis) were tested for anti-Fc gamma R activity using mouse rFc gamma RII in an ELISA. High reactivity compared to normal individuals was found for patients with all three diseases. The anti-Fc gamma R antibody was purified from several serum samples by affinity chromatography on a Sepharose column coupled with denatured, murine rFc gamma RII. Both IgM and IgG antibodies were found. To analyze the specificity of the affinity-purified autoantibody, cells (human neutrophils, IFN-gamma-stimulated neutrophils, monocytes, and the THP-1 monocytic cell line) that express different combinations of Fc gamma R (CD64, CD32, CD16) were stained with the affinity purified Ig. Ig directed against all three types of Fc gamma R were found. The results may reflect on the role of Fc gamma R-specific antibodies in the pathology of autoimmune diseases.
Antigens of varying size persist longer in subepithelial than in subendothelial immune deposits in murine glomeruli.
Authors: Mannik M , Kobayashi M , Alpers C E , Gauthier V J 
Published: December 2022

Abstract
The kinetics of removal of immune deposits from the subendothelial and subepithelial areas of glomeruli were analyzed in mice. Radiolabeled, cationized Ag of different molecular size, including human serum albumin, bovine thyroglobulin, and human IgM, were used to form the immune deposits in mouse glomeruli with specific, purified rabbit antibodies to these proteins. The disappearance curves of the radiolabeled Ag from glomeruli consisted of two exponential components. The immune deposits and their location in glomeruli were identified by immunofluorescence and electron microscopy. The t1/2 of disappearance of immune deposits were assigned to subendothelial or subepithelial deposits on the basis of ultrastructural observations. The t1/2 of subendothelial immune deposits ranged from 0.6 to 1.9 days with the three different Ag-antibody systems. In contrast, the t1/2 of the subepithelial immune deposits ranged from 9.32 to 231 days. The cationized human serum albumin in subepithelial areas had the longest t1/2, and this was not altered by the endogenous immune response to the injected materials, as determined in studies with nude mice. The results constitute formal documentation of the prolonged t1/2 of an exogenous Ag in glomerular immune deposits. The described approach can serve to examine variables that alter this prolonged presence of subepithelial immune deposits in glomeruli.
CD7- T cells represent a subset of normal human blood lymphocytes.
Authors: Reinhold U , Abken H , Kukel S , Moll M , Müller R , Oltermann I , Kreysel H W 
Published: December 2022

Abstract
In the peripheral blood of normal adults we identified a subpopulation of mature human T cells that lacks expression of CD7. These CD3+CD7- T cells represent 9% +/- 3.4 SD of PBMC as estimated by analyses of 38 different normal donors. The majority of CD7- T cells express TCR alpha/beta, and are of CD4 helper and CD45RO+CD45RA- "memory" phenotype as determined by three-color fluorescence analysis. We established seven CD4+CD7- T cell clones in vitro from purified CD7- blood T cells and compared these cells to CD4+CD7+ clones. Nonexpression and expression, respectively, of CD7 was a stable feature of all clones during long term culture for more than 6 mo. No CD7 mRNA could be detected by dot blot and Northern blot analysis of purified CD7- T cells and of expanded T cell clones implicating a transcriptional regulation of CD7 Ag expression. Ionomycin/TPA and PHA stimulation were not capable to induce CD7 expression in CD7- cells but up-regulated CD7 expression in CD7+ cells. Whereas CD7- cells of cutaneous T cell lymphoma exhibit a cerebriform nucleus (Sézary cells), no evidence was obtained for cerebriform nuclear morphology in normal CD7- T cells from peripheral blood. We suggest that these CD7- T cells represent a physiologic subset of mature T cells and may be the circulating counterpart of those lymphocytes that are found to be enriched in normal skin and in a variety of benign and malignant skin diseases.
cis-dominant regulation of CD4 and CD8 gene expression in rat/mouse T cell heterohybridomas.
Authors: Gocinski B L , Sun D , Coleclough C 
Published: December 2022

Abstract
To determine whether expression of CD4 and CD8 molecules on T cells is determined-solely by transacting regulators, we examined heterohybridomas derived from the fusion of a rat CD4+ T cell line and the CD4- CD8- mouse thymoma BW5147. The majority of hybrid offspring expressed rat CD4. However, a fraction of the cell lines obtained expressed not only rat CD4 but also various amounts of mouse CD4 and CD8 molecules from both species. Cloning of two of these heterogeneous lines revealed that expression of all four Ag varied not only between different clones but also within clonal populations. The expression of Ag not present on the parental cells suggested an alteration in the normally stable regulatory mechanisms present in those cells. Moreover, a lack of concordant expression between the rat and mouse loci was observed, indicating that active and silent homologous loci can exist together in single nuclei. Expression of CD4 and CD8 in these cells, therefore, cannot be solely mediated by trans-acting diffusible regulators but must also depend on cis-dominant effects on the loci themselves. The phenotypic heterogeneity of clonal populations was found to result from unpredictable shifts, both positive and negative, in the expression of CD4 and CD8 over time, indicating that the cis-dominant effects were only quasistable. Preliminary examinations of the density of 5-methylcytosine within the CD4 and CD8 loci in various phenotypic populations separated by FACS from within heterogeneous clones revealed a correlation between surface expression of the mouse CD8 protein and a lack of methylation around the mouse CD8 gene. In contrast, the CD4 gene remained extensively methylated regardless of its surface expression.
Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor.
Authors: Strassmann G , Masui Y , Chizzonite R , Fong M 
Published: December 2022

Abstract
In the colon-26 (C-26) tumor model, the cytokine IL-6 is an important factor involved in experimental cancer cachexia. Recent in vitro data indicated that IL-1 plays a role in the interaction between host macrophages and C-26 cells that express IL-1R, resulting in the amplification of tumor IL-6 production. To investigate the role of IL-1 on the development of C-26 cachexia in vivo, the effect of specific blockade of the action of IL-1 with reagents against IL-1R was evaluated. Both IL-1R antagonist (IL-1RA) and the mAb 35F5 directed against IL-1R type I, prevented binding of radioactive IL-1, and inhibited IL-1-induced IL-6 synthesis by the C-26 cell line. Whereas a systemic administration of these reagents did not reverse weight loss in C-26-bearing mice, intratumoral injections of IL-1RA significantly reduced cachexia. Furthermore, body composition analysis confirmed that this treatment improved lean tissue and fat, as well as hypoglycemia and serum IL-6 level. The fact that the treatment did not change the tumor burden suggests that it affected the host directly. These results support the hypothesis that, at the microenvironment of the C-26 tumor, IL-1 is involved in the cachexia endured by the host.