bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of lung inflammatory reactions in rats by an anti-human IL-8 antibody.
Authors: Mulligan M S , Jones M L , Bolanowski M A , Baganoff M P , Deppeler C L , Meyers D M , Ryan U S , Ward P A 
Published: December 2022

Abstract
IL-8 belongs to the family of chemotactic cytokines and may play an important role in the inflammatory response. In the current studies, a murine mAb (DM/C7) to human rIL-8 was found to have protective effects in inflammatory lung injury in rats. DM/C7 was nonreactive with the rat cytokine-induced neutrophil chemoattractant peptide. In vivo, DM/C7 blocked the glycogen-induced accumulation of neutrophils in rats and was highly protective against lung and dermal vascular injury after deposition of IgG immune complexes. The latter model of injury has recently been shown to be E-selectin dependent. The protective effects of DM/C7 correlated with reduced tissue accumulation of neutrophils, as measured by myeloperoxidase content. DM/C7 reacted with an epitope expressed by TNF-alpha-stimulated rat pulmonary artery endothelial cells and with the pulmonary vascular endothelium after intrapulmonary deposition of IgG immune complexes. In the model of IgG immune complex-induced lung injury, the protective effects of DM/C7 were abolished by prior absorption of the antibody with human rIL-8. Polyclonal antibody to cytokine-induced neutrophil chemoattractant peptide failed to protect against IgG immune complex-induced vascular injury even though this antibody blocked the in vitro chemotactic activity of cytokine-induced neutrophil chemoattractant. In the model of rapidly developing lung injury due to systemic activation of C after infusion of cobra venom factor, DM/C7 was not protective. As well, in the neutrophil-independent model of IgA immune complex-induced lung injury, treatment with DM/C7 was not protective. These data indicate that in inflammatory lung injury that is linked to E-selectin-dependent recruitment of neutrophils in rats, antibody to human IL-8 also blocks recruitment of neutrophils and thereby affords protection against lung injury. The data suggest the presence of an IL-8-like product in this model of lung injury.
Selective regulation of metalloproteinase inhibitor (TIMP-1) by oncostatin M in fibroblasts in culture.
Authors: Richards C D , Shoyab M , Brown T J , Gauldie J 
Published: December 2022

Abstract
Tissue inhibitor of metalloproteinases (TIMP-1) is a potent inhibitor of activated matrix metalloproteinases (MMP) such as collagenase, stromelysin, and gelatinase, and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells. Since various cytokines and growth factors can modify the production of MMP and TIMP-1, we explored the action of oncostatin M (OM), a unique lymphocyte- and monocyte-derived cytokine, on expression of these proteins. We examined the regulation of TIMP-1 expression in cultured human fibroblasts by cytokines including OM, IL-6, leukemia inhibitory factor (LIF), and IL-1 alpha. When used at levels of 5 to 50 ng/ml, OM, IL-6, LIF, and IL-1 alpha elevated the TIMP-1 expression at the RNA level in fibroblasts of lung or synovial origin. Interestingly, OM stimulation resulted in highest levels of TIMP-1 RNA and protein synthesis. However, unlike IL-1 alpha, the cytokines OM, IL-6, and LIF did not induce MMP or PGE2 release. OM also enhanced TIMP-1 mRNA levels in the H2981 lung carcinoma and HepG2 hepatoma cell lines. The results suggest that OM as well as IL-6 and LIF, other cytokines acting through similar receptor pathways, may act to inhibit net MMP activity by specifically up-regulating TIMP-1 expression. The selective induction of TIMP-1 by OM may be influential in altering matrix destruction in chronic inflammation and tumor metastasis.
Microbial superantigens induce NF-kappa B in the human monocytic cell line THP-1.
Authors: Trede N S , Castigli E , Geha R S , Chatila T 
Published: December 2022

Abstract
Staphylococcal superantigens bind to MHC class II molecules and induce transcriptional activation of IL-1 beta and TNF-alpha genes in human monocytic cells. The understanding of the mechanisms by which superantigens activate cytokine gene expression is incomplete. In this study, we demonstrate that toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins A and B induce the activation of NF-kappa B, a transcriptional enhancer that binds to sequences found in both the IL-1 beta and TNF-alpha promoters. Electrophoretic mobility-shift assays showed a rapid induction of nuclear proteins that bound to the consensus kappa B motif. Furthermore, TSST-1 potently stimulated chloramphenicol acetyltransferase (CAT) expression by THP-1 cells transfected with a consensus NF-kappa B-promoter CAT construct, indicative of induction of NF-kappa B enhancer function. Induction of both NF-kappa B DNA-binding proteins and NF-kappa B enhancer function was down-regulated by inhibitors of protein kinase C and protein tyrosine kinase, indicating a role for these protein kinases in the induction of NF-kappa B by MHC class II ligands. Using neutralizing antibodies, we demonstrated that after the stimulation of cells with TSST-1, TNF-alpha, but not IL-1 beta, acted to up-regulate binding of NF-kappa B to DNA and the activation of the NF-kappa B-promoter CAT construct. These results indicate that induction of NF-kappa B by superantigens is up-regulated in part by an autocrine loop involving TNF-alpha.
Molecular, biochemical, and functional characteristics of tumor necrosis factor-alpha produced by human placental cytotrophoblastic cells.
Authors: Yang Y , Yelavarthi K K , Chen H L , Pace J L , Terranova P F , Hunt J S 
Published: December 2022

Abstract
Previous studies have shown that the TNF-alpha gene is transcribed and translated in fully differentiated human placental syncytiotrophoblast. In this study, TNF transcripts were identified by in situ hybridization in cytotrophoblastic cells, a progenitor subpopulation that proliferates rapidly in early gestation tissues. To establish molecular and biochemical characteristics of cytotrophoblastic TNF and to evaluate potential utilization, experiments were conducted on two cytotrophoblastic cell lines, Jar and JEG-3. Northern blot hybridization and immunocytochemical tests showed that Jar and JEG-3 cells contained TNF mRNA and specific protein. Enzyme immunoassays demonstrated production of TNF, and immunoprecipitation experiments showed that Jar cell TNF protein was the same molecular mass as macrophage TNF. DNA synthesis in both lines was promoted by rTNF, and experiments employing 17-mer TNF antisense and sense oligonucleotides showed specific inhibition of DNA synthesis by antisense sequences. Both p60 and p80 TNF-R mRNA were present in the choriocarcinoma cell lines, and DNA synthesis was inhibited by antibody to the p60 TNF-R. Although the two lines were similar in many respects, Jar cells produced more TNF and demonstrated a greater reliance on TNF for their growth. Collectively, the results indicate that: 1) the TNF gene is expressed in both normal and malignant cytotrophoblast; 2) certain molecular, immunologic, and biochemical characteristics of trophoblast-derived TNF are similar to macrophage TNF; and 3) the p60 TNF-R facilitates utilization of TNF as an autocrine growth factor by choriocarcinoma cells. Although TNF apparently serves important functions in cytotrophoblast during the course of placental development that might include promotion of proliferation and invasion, constitutive expression of this gene in neoplastic cells could account in part for the remarkable ability of trophoblastic tumors to overcome host defenses.
Antibody-mediated redistribution and shedding of endothelial antigens in the rabbit.
Authors: Yuzawa Y , Brentjens J R , Brett J , Caldwell P R , Esposito C , Fukatsu A , Godman G , Stern D , Andres G 
Published: December 2022

Abstract
We report the results of studies performed in vitro and in vivo that were designed to explore individual, sequential, and concurrent Ag-antibody interactions at the surface of rabbit endothelial cells. Divalent heterologous antibodies to rabbit lung angiotensin-converting enzyme and to rabbit lung thrombomodulin were employed. In cultured monolayers, both antibodies redistributed the specific Ag and co-redistributed the immunologically unrelated Ag inducing partial or complete disappearance of the Ag from the cell surface (antigenic modulation) in 15 to 60 min. When injected into living rabbits, each antibody induced a rapid (1 to 3 min) redistribution and subsequent modulation of the specific and of the unrelated Ag at the surface of alveolar endothelial cells. Immune complexes, and the unrelated Ag, were shed in the circulation, attaining peak levels 3 to 4 min after the injection; were rapidly bound by platelets, E, and polymorphonuclear leukocytes; and were subsequently found in phagocytic cells in the spleen and in the liver. Thrombomodulin co-shed by angiotensin-converting enzyme antibody and, to a lesser degree, angiotensin-converting enzyme co-shed by thrombomodulin antibody, crossed the glomerular capillary walls and were reabsorbed by the epithelial cells of the proximal tubules within 2 to 3 min. The results show that immunologically unrelated Ag can be passively entrapped during formation of immune complexes at the cell surface, and provide new information on the kinetics of clearance of immune complexes containing endogenous, structural Ag.
Construction of an HIV-1 peptide vaccine containing a multideterminant helper peptide linked to a V3 loop peptide 18 inducing strong neutralizing antibody responses in mice of multiple MHC haplotypes after two immunizations.
Authors: Ahlers J D , Pendleton C D , Dunlop N , Minassian A , Nara P L , Berzofsky J A 
Published: December 2022

Abstract
Peptide constructs comprised of multideterminant Th peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52 to 73% of HIV positive, Ag-responsive patients, were colinearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB. The segments containing clusters of overlapping Th epitopes were called cluster peptides. Cognate help for peptide 18 antibody was elicited after a single immunization in all strains of mice that had previously responded to a T cell epitope encompassed by the cluster peptides. Animals boosted with cluster peptide-peptide 18 constructs 36 to 52 wk later displayed secondary antibody responses. Cluster peptide 3-peptide 18 induced antibody that neutralized homologous virus in one strain of mice although strong peptide 18 antibody responses were detected in all four strains of mice. The most promising construct, cluster peptide 6-peptide 18, induced neutralizing antibody in all strains of mice tested, and in two strains the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, antibody titers for 90% neutralization in the range of 1/1000 to 1/16,000 were achieved. These neutralizing titers against the homologous viral strain, after just two immunizations, are at least four- to eightfold higher than the highest titered other polyclonal V3-specific immune sera we have ever observed in our laboratories. We also asked why some sera neutralized and others with similar ELISA titers did not. No correlation was found between neutralization and isotype or affinity for peptide or gp 120. We could not account for neutralization by antibodies to the helper sites. Substitutions made in the central loop region of peptide 18, amino acid residues PGRAF, dramatically reduced binding of both neutralizing and non-neutralizing sera although some fine specificity differences between neutralizing and nonneutralizing sera were noted. These results have implications for the design of synthetic peptide vaccines for HIV.
Identification and propagation of a putative immunosuppressive orphan parvovirus in cloned T cells.
Authors: McKisic M D , Lancki D W , Otto G , Padrid P , Snook S , Cronin D C , Lohmar P D , Wong T , Fitch F W 
Published: December 2022

Abstract
A putative parvovirus related to minute virus of mice (MVM), but distinct from MVM-prototype and MVM-immunosuppressive, was identified, using serologic techniques and Southern blot analysis, in maintenance cultures of established T cell clones. This putative viral agent resulted in a lytic infection of cloned L3 cytotoxic T cells but was unable to produce a productive infection in BHK.21 or EL-4(G) cells. Moreover, maintenance cultures of several distinct subsets of cloned T cells apparently contaminated with this putative viral agent contained poorly growing cells and erythrocyte aggregates. The aggregation of mouse erythrocytes appeared to be a reliable indicator of infection with this putative virus and may be related to the ability of this agent to agglutinate mouse erythrocytes. This putative virus also was found to inhibit the proliferative response of certain cloned T cells to IL-2 and Ag. Viremic mice and secondary MLC supernatant were identified as two potential sources of contamination and represent ways of propagating this agent in vitro. The finding that this agent interferes with the ability of T cell clones to thrive and, therefore has the potential to alter immune responses, emphasizes the importance of identifying and excluding parvoviral infections in cultures of murine T lymphocytes.
Both CD45RA+ and CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells.
Authors: Okumura M , Fujii Y , Inada K , Nakahara K , Matsuda H 
Published: December 2022

Abstract
Expression of CD45 isoforms and some adhesion molecules on T cells change during T cell activation. In CD4+ T cells, it has been reported that CD45RA is lost and CD45RO is up-regulated when CD4+ T cells are stimulated. This change seemed to be irreversible and thus CD45RA may serve as a marker for virgin T cells and CD45R0 as a marker for memory T cells in CD4+ T cells. In CD8+ T cells, however, the expression of CD45 isoform has been less well understood. We have previously reported the switching of CD45 isoform expression may be reversible and CD8+CD45RA+ T cells may contain preactivated T cells. We present further evidence to support this notion by investigating the expression of lymphocyte function-associated Ag (LFA-1) in relation to CD45 isoform expression in various T cell populations in the human. In the thymus and umbilical cord blood, more than 97% of both CD4+ and CD8+ single positive T cells expressed LFA-1 at a low level. In CD4+ peripheral blood T cells, a high level of LFA-1 expression was found only in the CD45RA- population: 98% of CD45RA+ cells were LFA-1low. In CD8+ peripheral blood T cells, in contrast, a distinct population of LFA-1high cells was found in CD45RA+ subset, comprising about 45% of this subset in a 32-yr-old donor. In 7 days after stimulation with PHA, all CD4+ and CD8+ T cells, irrespective of their CD45 isoform expression, were LFA-1high. The proportion of CD45RA+ cells decreased in CD4+ but slightly increased in CD8+ T cells after the stimulation. These results support the notion that CD45RA and CD45R0 mark virgin and memory T cells respectively in the CD4+ T cells, and that CD8+CD45RA- T cells are primed. However, the validity of CD45RA as a marker of virgin cells in CD8+ T cells is seriously questioned.
Characterization of endogenous peptides bound to purified HLA-DR molecules and their absence from invariant chain-associated alpha beta dimers.
Authors: Newcomb J R , Cresswell P 
Published: December 2022

Abstract
We have examined peptides bound in vivo to DR alpha beta dimers and alpha beta-Invariant (I) chain complexes purified directly from a DR11, DRw52 homozygous B lymphoblastoid cell line. Nine major peptides were purified by reversed-phase HPLC from cell derived alpha beta dimers and sequenced. Eight of these were from known sources, including both endogenously synthesized and exogenous proteins. The endogenously derived peptides originated from secretory proteins, from the extracytoplasmic regions of transmembrane proteins, and from heat shock proteins. All of the peptides were from 13 to 16 amino acids in length. Comparison of the sequences of a subset of these DR-associated peptides with those of other reported DR-binding peptides suggests that an aromatic amino acid followed by a basic amino acid seven residues C-terminal from it may provide a generalizable, but not absolute, DR-binding motif, with additional residues possibly contributing to DR allelic specificity. In contrast to the alpha beta dimers, no peptides were detected bound to purified alpha beta I complexes. These data suggest that I chain-associated alpha beta dimers within the cell do not bind peptides, and provide in vivo evidence that I chain prevents the binding of inappropriate peptides to class II molecules during early stages of transport.
Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. Characterization of thyroiditis-inducing T cell lines and clones derived from thyroid lesions.
Authors: Sugihara S , Fujiwara H , Shearer G M 
Published: December 2022

Abstract
We have previously shown that autoimmune thyroiditis spontaneously develops in T cell-depleted (C57BL/6xC3H/He)F1 mice after adoptive transfer of syngeneic lymphoid cells that have been depleted of CD5bright T lymphocytes. This mouse model was considered to be an instructive model for Hashimoto's thyroiditis in humans, and suggested that CD5dull CD4+ autoreactive T cells are not deleted in normal lymphoid cell populations and induce thyroiditis after elimination of regulatory T cell subsets. In our study, we have established thyroid-derived T cell lines and clones by culturing thyroid-infiltrating lymphocytes with thyroid epithelial cells and syngeneic feeder cells in the presence of exogenous IL-2. Both CD4+ T cells and CD8+ T cells were identified and their CD5 expression was dull or negative. In our report, we focused on CD4+ T cells. Four CD4+ T cell lines and 19 clones were generated and characterized. CD4+ T cell clones derived from F1 hybrid (H-2b/k) mice responded to thyroid Ag in the context of not only class II MHC molecules from both parental strains (I-Ak or I-Ab), but also F1 unique MHC molecules. Thyroglobulin (Tg) was demonstrated to be a major autoantigen of the thyroid for T cell responses, and at least two epitopes of Tg were suggested to be recognized by T cell clones. An additional undefined thyroid component other than Tg was recognized by some T cell clones. Thyroid-derived T cells were all TCR-alpha beta+. Five types of V beta usage (V beta 2, 4, 8.3, 14, and an undefined V beta) were found in CD4+ T cells. Finally, the thyroid lesions could be transferred to syngeneic mice by five distinct groups of CD4+ T cell clones, which were distinguished on the basis of their Ag specificity, MHC restriction, and TCRV beta usage. The considerable heterogeneity of TCRV beta usage of thyroiditis-inducing T cell clones in this study may be attributed to the multiple patterns of their recognition of the thyroid autoantigens. These findings provide important implications for further understanding of organ-specific autoimmune processes induced by depletion of regulatory T cell subsets.
Soluble complement receptor type 1 prevents human complement-mediated damage of the rabbit isolated heart.
Authors: Homeister J W , Satoh P S , Kilgore K S , Lucchesi B R 
Published: December 2022

Abstract
The purpose of this study was to determine if recombinant human soluble CR1 (sCR1) could prevent tissue damage associated with the activation of human complement. Directly mediated human complement-dependent myocardial injury was induced in the rabbit isolated heart perfused with a Krebs-Henseleit buffer containing 6% human plasma. There were three study groups: 1) 6% heat-inactivated human plasma (control); 2) 6% normal human plasma (NHP); or 3) 6% normal human plasma + 20 nM sCR1 (NHP + sCR1). Recorded functional parameters of the control group remained stable throughout the duration of the 70-min protocol. Complement activation in hearts perfused with 6% NHP increased the diastolic pressure; decreased developed pressure; and increased coronary perfusion pressure. These alterations were accompanied by a decrease in the maximum positive and negative dP/dt. Complement activation also increased cardiac muscle lymphatic fluid flow rate. The changes were greatest between 20 and 40 min, but persisted for the duration of the protocol. sCR1 (20 nM) in the perfusate containing 6% NHP prevented the complement-mediated alterations in the systolic, developed, and coronary perfusion pressures. sCR1 prevented the decrement in the positive and negative dP/dt, and the increase in the lymphatic fluid flow rate. Values for each of these parameters in hearts perfused with 6% NHP + sCR1 were not altered from those of controls at any time point in the protocol. Ultrastructural changes were present in tissues perfused with 6% NHP along with immunohistochemical evidence for presence of the terminal C5b-9 complex. sCR1 prevented the ultrastructural changes and the formation of the terminal complex. sCR1 offers significant protection against the cytolytic effects resulting from activation of the human complement system.
Antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 prevent glomerular injury in rat experimental crescentic glomerulonephritis.
Authors: Kawasaki K , Yaoita E , Yamamoto T , Tamatani T , Miyasaka M , Kihara I 
Published: December 2022

Abstract
The involvement of adhesion molecules in the glomerular accumulation of inflammatory cells and subsequent glomerular injury was examined in WKY rats with nephrotoxic serum nephritis. This model is characterized by early infiltration of CD8-positive NK cells, followed by influx of monocytes/macrophages into the glomeruli. At day 1 and later, up-regulated expression of intercellular adhesion molecule-1 (ICAM-1) was observed exclusively in the glomerular endothelial cells in association with the influx of CD8-positive cells and monocytes/macrophages. These cells expressed lymphocyte function-associated Ag-1 (LFA-1). Repeated injection of mAb against rat ICAM-1 or alpha-subunit of LFA-1 (LFA-1 alpha) dose dependently prevented the development of proteinuria, the influx of these cells, and subsequent crescent formation in this nephrotoxic serum nephritis model. Furthermore, simultaneous administration of anti-ICAM-1 mAb and anti-LFA-1 alpha mAb exerted additive protective effects against urinary protein excretion and crescentic glomerulonephritis. Binding of anti-GBM antibody to the glomeruli and production of circulating anti-rabbit IgG antibody were unaffected by injection of these mAb. These results indicate that adhesion of CD8-positive cells and monocytes to glomerular endothelial cells through the LFA-1/ICAM-1 pathway is crucial for the initiation and subsequent progression of nephrotoxic serum nephritis in WKY rats.