bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipopolysaccharide Binding Protein and Serum Amyloid A Secretion by Human Intestinal Epithelial Cells During the Acute Phase Response
Authors: Vreugdenhil Anita C. E. , Dentener Mieke A. , Snoek A. M. Patricia , Greve Jan-Willem M. , Buurman Wim A. 
Published: December 2022

AbstractThe acute phase proteins LPS binding protein (LBP) and serum amyloid A (SAA) are produced by the liver and are present in the circulation. Both proteins have been shown to participate in the immune response to endotoxins. The intestinal mucosa forms a large surface that is continuously exposed to these microbial products. By secretion of antimicrobial and immunomodulating agents, the intestinal epithelium contributes to the defense against bacteria and their products. The aim of this study was to explore the influence of the inflammatory mediators TNF-α, IL-6, and IL-1β on the release of LBP and SAA by intestinal epithelial cells (IEC). In addition, the induction of LBP and SAA release by cell lines of intestinal epithelial cells and hepatic cells was compared. The data obtained show that in addition to liver cells, IEC also expressed LBP mRNA and released bioactive LBP and SAA upon stimulation. Regulation of LBP and SAA release by IEC and hepatocytes was typical for class 1 acute phase proteins, although differences in regulation between the cell types were observed. Endotoxin did not induce LBP and SAA release. Glucocorticoids were demonstrated to strongly enhance the cytokine-induced release of LBP and SAA by IEC, corresponding to hepatocytes. The data from this study, which imply that human IEC can produce LBP and SAA, suggest a role for these proteins in the local defense mechanism of the gut to endotoxin. Furthermore, the results demonstrate that tissues other than the liver are involved in the acute phase response.
Stem Cell Factor Is Localized in, Released from, and Cleaved by Human Mast Cells
Authors: de Paulis Amato , Minopoli Giuseppina , Arbustini Eloisa , de Crescenzo Gennaro , Dal Piaz Fabrizio , Pucci Piero , Russo Tommaso , Marone Gianni 
Published: December 2022

AbstractStem cell factor (SCF) is the most important cytokine regulating human mast cell growth and functions. The immunogold technique showed SCF in the secretory granules of skin mast cells and in lung parenchymal mast cells (HLMC). Immunoreactive SCF (iSCF) was detected in cell lysates of HLMC, but not in basophils; iSCF and histamine were detected in supernatants of HLMC 3 min after challenge with anti-FcεRI or anti-IgE, and iSCF in supernatants rapidly declined after 30 min, whereas histamine remained unchanged for 120 min. HPLC and electrospray mass spectrometry (ES/MS) analysis of recombinant human SCF1–166 (18,656.9 ± 0.9 Da) treated with chymase showed a polypeptide of 17,977.1 ± 0.6 Da and a minor component of 697.4 ± 0.1 Da generated by specific cleavage at Phe159. SCF1–166 and SCF1–159 similarly activated HLMC, potentiated anti-IgE-induced activation of these cells, and stimulated HLMC chemotaxis. SCF159–166 had no effect on mast cells. Western blot analysis of supernatants of anti-IgE-activated HLMC incubated with recombinant human SCF1–166 showed that SCF1–166 was rapidly cleaved to SCF1–159 and SCF1–144. Experiments with supernatants of anti-IgE-activated HLMC incubated with SCF1–166 yielded similar results. In conclusion, SCF is stored in mast cell secretory granules and is immunologically released by human mast cells. SCF1–166 is rapidly and specifically cleaved to SCF1–159 by chymase, which retains its biological effect on mast cells. SCF is also cleaved by other proteases to several SCF species whose possible biological activities remain to be established.
Inhibition of Murine Neutrophil Recruitment In Vivo by CXC Chemokine Receptor Antagonists
Authors: McColl Shaun R. , Clark-Lewis Ian 
Published: December 2022

Abstract
In this study, we have examined the ability of chemokine receptor antagonists to prevent neutrophil extravasation in the mouse. Two murine CXC chemokines, macrophage-inflammatory protein (MIP)-2 and KC, stimulated the accumulation of leukocytes into s.c. air pouches, although MIP-2 was considerably more potent. The leukocyte infiltrate was almost exclusively neutrophilic in nature. A human CXC chemokine antagonist, growth-related oncogene (GRO)-α(8–73), inhibited calcium mobilization induced by MIP-2, but not by platelet-activating factor in leukocytes isolated from the bone marrow, indicating that this antagonist inhibits MIP-2 activity toward murine leukocytes. Pretreatment of mice with GROα(8–73) inhibited, in a dose-dependent manner, the MIP-2-induced influx of neutrophils to levels that were not significantly different from control values. Moreover, this antagonist was also effective in inhibiting the leukocyte recruitment induced by TNF-α, LPS, and IL-1β. Leukocyte infiltration into the peritoneal cavity in response to MIP-2 was also inhibited by prior treatment of mice with GROα(8–73) or the analogue of platelet factor 4, PF4(9–70). The results of this study indicate 1) that the murine receptor for MIP-2 and KC, muCXCR2, plays a major role in neutrophil recruitment to s.c. tissue and the peritoneal cavity in response to proinflammatory agents and 2) that CXCR2 receptor antagonists prevent acute inflammation in vivo.
Acceleration and Increased Severity of Collagen-Induced Arthritis in P-Selectin Mutant Mice
Authors: Bullard Daniel C. , Mobley James M. , Justen James M. , Sly Laurel M. , Chosay John G. , Dunn Colin J. , Lindsey J. Russell , Beaudet Arthur L. , Staite Nigel D. 
Published: December 2022

Abstract
P-selectin plays an important role in leukocyte adherence to microvascular endothelium and is expressed in synovial tissue from patients with rheumatoid arthritis (RA). However, the contribution of P-selectin to the initiation and chronicity of joint inflammation is not well understood. In these studies, collagen-induced arthritis (CIA) was induced in P-selectin mutant (−/−) mice to explore the role of P-selectin in the development of joint inflammation. Surprisingly, CIA onset was accelerated and severity was increased in P-selectin mutant mice, compared with wild-type mice (+/+). Increased levels of anti-type II collagen IgG were detected in both nonarthritic and arthritic P-selectin mutant mice from days 14–91. In addition, splenocytes isolated from immunized and nonimmunized P-selectin mutant mice produced significantly less IL-2 and IL-4, but significantly higher levels of IL-10 and IL-5 than splenocytes from wild-type mice. These observations show that P-selectin-mediated leukocyte rolling is not required for the development of murine CIA and that P-selectin expression exerts a controlling effect on the development of Ag-driven inflammatory joint disease, possibly by mediating the recruitment and/or trafficking of specific leukocyte subtypes into lymphoid tissue or inflammatory foci.
Endothelial α2,6-Linked Sialic Acid Inhibits VCAM-1- Dependent Adhesion Under Flow Conditions
Authors: Abe Yasunori , Smith C. Wayne , Katkin Julie P. , Thurmon Lisa M. , Xu Xudong , Mendoza Leonardo H. , Ballantyne Christie M. 
Published: December 2022

AbstractWe have previously shown that costimulation of endothelial cells with IL-1 + IL-4 markedly inhibits VCAM-1-dependent adhesion under flow conditions. We hypothesized that sialic acids on the costimulated cell surfaces may contribute to the inhibition. Northern blot analyses showed that Galβ1-4GlcNAc α2,6-sialyltransferase (ST6N) mRNA was up-regulated in cultured HUVEC by IL-1 or IL-4 alone, but that the expression was enhanced by costimulation, whereas the level of Galβ1-4GlcNAc/Galβ1-3GalNAc α2,3-sialyltransferase (ST3ON) mRNA was unchanged. Removing both α2,6- and α2,3-linked sialic acids from IL-1 + IL-4-costimulated HUVEC by sialidase significantly increased VCAM-1-dependent adhesion, whereas removing α2,3-linked sialic acid alone had no effect; adenovirus-mediated overexpression of ST6N with costimulation almost abolished the adhesion, which was reversible by sialidase. The same treatments of IL-1-stimulated HUVEC had no effect. Lectin blotting showed that VCAM-1 is decorated with α2,6- but not α2,3-linked sialic acids. However, overexpression of α2,6-sialyltransferase did not increase α2,6-linked sialic acid on VCAM-1 but did increase α2,6-linked sialic acids on other proteins that remain to be identified. These results suggest that α2,6-linked sialic acids on a molecule(s) inducible by costimulation with IL-1 + IL-4 but not IL-1 alone down-regulates VCAM-1-dependent adhesion under flow conditions.
Eotaxin Potentiates Antigen-Dependent Basophil IL-4 Production
Authors: Devouassoux Gilles , Metcalfe Dean D. , Prussin Calman 
Published: December 2022

AbstractBasophils are a major source of IL-4, which is a critical factor in the generation of allergic inflammation. Eotaxin induces chemotaxis mediated through the CC chemokine receptor 3 (CCR3) present on basophils as well as eosinophils and Th2 cells, thereby promoting cell recruitment. To determine whether eotaxin has other proinflammatory activity, we examined the effect of eotaxin on basophil IL-4 expression by flow cytometry. Eotaxin alone had no effect on basophil IL-4 production, but further increased allergen-stimulated IL-4 expression. Eotaxin also enhanced IL-4 release from purified basophils 2- to 4-fold, as determined by ELISA (p &lt; 0.01). Addition of eotaxin to cultures resulted in a 40-fold left shift in the dose response to Ag. This effect was obtained with physiologic concentrations of eotaxin (10 ng/ml), was abrogated by an Ab to the CCR3 receptor, and was noted with other chemokine ligands of CCR3. Additionally, eotaxin augmented IL-3 priming of basophil IL-4 production in a synergistic manner (p &lt; 0.01). In contrast, no priming was observed with either IL-5 or GM-CSF. These results establish a novel function for eotaxin and other chemokine ligands of CCR3: the potentiation of Ag-mediated IL-4 production in basophils, and suggest a potential nonchemotactic role for CC chemokines in the pathogenesis and amplification of inflammation.
Inducible Expression and Regulation of the α1-Acid Glycoprotein Gene by Alveolar Macrophages: Prostaglandin E2 and Cyclic AMP Act as New Positive Stimuli
Authors: Fournier Thierry , Bouach Najet , Delafosse Christian , Crestani Bruno , Aubier Michel 
Published: December 2022

AbstractWe have reported that α1-acid glycoprotein (AGP) gene expression was induced in lung tissue and in alveolar type II cells during pulmonary inflammatory processes, suggesting that local production of this immunomodulatory protein might contribute to the modulation of inflammation within the alveolar space. Because AGP may also be secreted by other cell types in the alveolus, we have investigated the expression and the regulation of the AGP gene in human and rat alveolar macrophages. Spontaneous AGP secretion by alveolar macrophages was increased 4-fold in patients with interstitial lung involvement compared with that in controls. In the rat, immunoprecipitation of [35S]methionine-labeled cell lysates showed that alveolar macrophages synthesize and secrete AGP. IL-1β had no effect by itself, but potentiated the dexamethasone-induced increase in AGP production. RNase protection assay demonstrated that AGP mRNA, undetectable in unstimulated cells, was induced by dexamethasone. Conditioned medium from LPS-stimulated macrophages as well as IL-1β had no effect by themselves, but potentiated the dexamethasone-induced increase in AGP mRNA levels. In addition to cytokines, PGE2 as well as dibutyryl cAMP increased AGP mRNA levels in the presence of dexamethasone. When AGP expression in other cells of the monocyte/macrophage lineage was examined, weak and no AGP production by human blood monocytes and by rat peritoneal macrophages, respectively, were observed. Our data showed that 1) AGP expression is inducible specifically in alveolar macrophages in vivo and in vitro; and 2) PGE2 and cAMP act as new positive stimuli for AGP gene expression.
Signaling Functions of L-Selectin in Neutrophils: Alterations in the Cytoskeleton and Colocalization with CD18
Authors: Simon Scott I. , Cherapanov Vera , Nadra Imad , Waddell Tom K. , Seo Scott M. , Wang Qin , Doerschuk Claire M. , Downey Gregory P. 
Published: December 2022

AbstractLigation and clustering of L-selectin by Ab (“cross-linking”) or physiologic ligands results in activation of diverse responses that favor enhanced microvascular sequestration and emigration of neutrophils. The earliest responses include a rise in intracellular calcium, enhanced tyrosine phosphorylation, and activation of extracellular signal-regulated kinases. Additionally, cross-linking of L-selectin induces sustained shape change and activation of β2 integrins, leading to neutrophil arrest under conditions of shear flow. In this report, we examined several possible mechanisms whereby transmembrane signals from L-selectin might contribute to an increase in the microvascular retention of neutrophils and enhanced efficiency of emigration. In human peripheral blood neutrophils, cross-linking of L-selectin induced alterations in cellular biophysical properties, including a decrease in cell deformability associated with F-actin assembly and redistribution, as well as enhanced adhesion of microspheres bound to β2 integrins. L-selectin and the β2 integrin became spatially colocalized as determined by confocal immunofluorescence microscopy and fluorescence resonance energy transfer. We conclude that intracellular signals from L-selectin may enhance the microvascular sequestration of neutrophils at sites of inflammation through a combination of cytoskeletal alterations leading to cell stiffening and an increase in adhesiveness mediated through alterations in β2 integrins.
Identification of Five MAGE-A1 Epitopes Recognized by Cytolytic T Lymphocytes Obtained by In Vitro Stimulation with Dendritic Cells Transduced with MAGE-A1
Authors: Chaux Pascal , Luiten Rosalie , Demotte Nathalie , Vantomme Valérie , Stroobant Vincent , Traversari Catia , Russo Vincenzo , Schultz Erwin , Cornelis Guy R. , Boon Thierry , van der Bruggen Pierre 
Published: December 2022

Abstract
MAGE genes are expressed by many human tumors of different histological types but not by normal cells, except for male germline cells. The Ags encoded by MAGE genes and recognized by T cells are therefore strictly tumor-specific. Clinical trials involving therapeutic vaccination of cancer patients with MAGE antigenic peptides or proteins are in progress. To increase the range of patients eligible for therapy with peptides, it is important to identify additional MAGE epitopes recognized by CTL. Candidate peptides known to bind to a given HLA have been used to stimulate T lymphocytes in vitro. In some instances, CTL clones directed against these synthetic peptides have been obtained, but these clones often failed to recognize tumor cells expressing the relevant gene. Therefore, we designed a method to identify CTL epitopes that selects naturally processed peptides. Monocyte-derived dendritic cells infected with a recombinant canarypoxvirus (ALVAC) containing the entire MAGE-A1 gene were used to stimulate CD8+ T lymphocytes from the blood of individuals without cancer. Responder cell microcultures that specifically lysed autologous cells expressing MAGE-A1 were cloned using autologous stimulator cells either transduced with a retrovirus coding for MAGE-A1 or infected with recombinant Yersinia-MAGE-A1 bacteria. The CTL clones were tested for their ability to lyse autologous cells loaded with each of a set of overlapping MAGE-A1 peptides. This strategy led to the identification of five new MAGE-A1 epitopes recognized by CTL clones on HLA-A3, -A28, -B53, -Cw2, and -Cw3 molecules. All of these CTL clones recognized target cells expressing gene MAGE-A1.
Experimental Autoimmune Encephalomyelitis in NF-κB- Deficient Mice: Roles of NF-κB in the Activation and Differentiation of Autoreactive T Cells
Authors: Hilliard Brendan , Samoilova Elena B. , Liu Tzu-Shang T. , Rostami Abdolmohamad , Chen Youhai 
Published: December 2022

Abstract
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the CNS, which has long been used as an animal model for human multiple sclerosis. Development of autoimmune disease requires coordinated expression of a number of genes that are involved in the activation and effector functions of inflammatory cells. These include genes that encode costimulatory molecules, cytokines, chemokines, and adhesion molecules. Activation of these genes is regulated at the transcriptional level by several families of transcription factors. One of these is the NF-κB family, which is present in a variety of cell types and becomes highly activated at sites of inflammation. To test the roles of NF-κB in the development of autoimmune diseases, we studied EAE in mice deficient in one of the NF-κB isoforms, i.e., NF-κB1 (p50). We found that NF-κB1-deficient mice were significantly resistant to EAE induced by myelin oligodendrocyte glycoprotein. The resistance was primarily evidenced by a decrease in disease incidence, clinical score, and the degree of CNS inflammation. Furthermore, we established that the resistance to EAE in NF-κB1-deficient mice was associated with a deficiency of myelin oligodendrocyte glycoprotein-specific T cells to differentiate into either Th1- or Th2-type effector cells in vivo. These results strongly suggest that NF-κB1 plays crucial roles in the activation and differentiation of autoreactive T cells in vivo and that blocking NF-κB function can be an effective means to prevent autoimmune encephalomyelitis.
HIV-1 Tat Induces Monocyte Chemoattractant Protein-1-Mediated Monocyte Transmigration Across a Model of the Human Blood-Brain Barrier and Up-Regulates CCR5 Expression on Human Monocytes
Authors: Weiss Jonathan M. , Nath Avindra , Major Eugene O. , Berman Joan W. 
Published: December 2022

Abstract
AIDS dementia is characterized by neuronal loss in association with synaptic damage. A central predictor for clinical onset of these symptoms is the infiltration of monocytes and macrophages into CNS parenchyma. Chronic HIV-1 infection of monocytes also allows these cells to serve as reservoirs for persistent viral infection. Using a coculture of endothelial cells and astrocytes that models several aspects of the human blood-brain barrier, we examined the mechanism whereby the HIV-derived factor Tat may facilitate monocyte transmigration. We demonstrate that treatment of cocultures on the astrocyte side with HIV-1 Tat induced significant monocyte chemoattractant protein (MCP)-1 protein. Astrocytes, but not endothelial cells, were the source of this MCP-1 expression. Supernatants from Tat-treated cocultures induced significant monocyte transmigration, which was detected by 2.5 h after the addition of PBMC. Pretreatment of the supernatants from Tat-stimulated cocultures with an Ab to MCP-1 completely blocked monocyte transmigration. Flow cytometric analysis of Tat-stimulated PBMC demonstrated that Tat up-regulated expression of the chemokine receptor, CCR5, on monocytes in a time-dependent manner. Taken together, our data indicate that HIV-1 Tat may facilitate the recruitment of monocytes into the CNS by inducing MCP-1 expression in astrocytes. These recruited monocytes may contribute to the pathogenesis of HIV-1-associated AIDS encephalitis and dementia.
A Dominant Role for the Thymus and MHC Genes in Determining the Peripheral CD4/CD8 T Cell Ratio in the Rat
Authors: Damoiseaux Jan G. M. C. , Cautain Bastien , Bernard Isabelle , Mas Magali , van Breda Vriesman Peter J. C. , Druet Philippe , Fournié Gilbert , Saoudi Abdelhadi 
Published: December 2022

AbstractDuring their development, immature CD4CD8 double positive thymocytes become committed to either the CD4 or CD8 lineage. The final size of the peripheral CD4 and CD8 T cell compartments depends on thymic output and on the differential survival and proliferation of the respective T cell subsets in the periphery. Our results reveal that the development of the distinct peripheral CD4/CD8 T cell ratio between Lewis and Brown Norway rats originates in the thymus and, as shown by the use of radiation bone marrow chimeras, is determined by selection on radio-resistant stromal cells. Furthermore, this difference is strictly correlated with the MHC haplotype and is the result of a reduction in the absolute number of CD8 T cells in Brown Norway rats. These data suggest that the distinct CD4/CD8 T cell ratio between these two rat strains is the consequence of differential interactions of the TCR/CD8 coreceptor complex with the respective MHC class I haplotypes during selection in the thymus.
Differential Coupling of Second Signals for Cytotoxicity and Proliferation in CD8+ T Cell Effectors: Amplification of the Lytic Potential by B7
Authors: Krummel Matthew F. , Heath William R. , Allison Janette 
Published: December 2022

AbstractThe role of second signals delivered through B7/CD28 interactions in T cell activation is well documented. However, once CTLs are elicited, TCR-mediated cytotoxicity appears to be uncoupled from the requirement for costimulatory signals. In this study, we show an uncoupling across a broad range of concentrations of peptide, thus demonstrating that cytolysis is a TCR-mediated response that is fully independent of costimulatory signals. However, the same T cell effectors remain fully responsive to B7 engagement, which is able to amplify Ag-mediated proliferation and cytolytic capacity. B7 expression by targets results in an IL-2-mediated proliferative expansion of the effectors concurrent with the elimination of the targets. Thus, costimulation of effectors results in a vast expansion in lytic units over time, which does not occur in the absence of IL-2 or B7. Both TCR-derived and second signals appear to be necessary to achieve this result. These results suggest that B7-expressing APC or a cohort of IL-2-producing helper cells would functionally extend the duration and effectiveness of the cytotoxic response occurring in localized immune responses.
Intracellular Signaling of gp34, the OX40 Ligand: Induction of c-junand c-fosmRNA Expression Through gp34 upon Binding of Its Receptor, OX40
Authors: Matsumura Yumi , Hori Toshiyuki , Kawamata Shin , Imura Akihiro , Uchiyama Takashi 
Published: December 2022

AbstractWe investigated the intracellular signaling events of OX40 ligand (gp34), a member of the TNF family. To elucidate the intracellular signaling via gp34, we prepared a model system in which a human gp34-transfected mouse epithelial cell line was stimulated with a recombinant soluble form of OX40. We demonstrated that OX40 binding resulted in increase in c-jun and c-fos mRNA levels in this transfectant by Northern blot analysis, which was blocked by the pretreatment with anti-gp34 Ab. The studies with various gp34 deletion mutants showed that the cytoplasmic portion including the amino acid sequence 16–21 (RPRFER) was required for the induction of c-jun and c-fos mRNA expression. Furthermore, OX40 binding induced c-jun mRNA expression also in HUVECs, which in our previous study have been shown to express gp34 and interact with activated T cells through the OX40/gp34 pathway. On the other hand, c-fos mRNA was detectable neither in unstimulated HUVECs nor in gp34-stimulated HUVECs. These results indicate that the OX40/gp34 system generates two-way signals and may elicit biological effects on vascular endothelial cells.