bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gallium Arsenide Modulates Proteolytic Cathepsin Activities and Antigen Processing by Macrophages
Authors: Lewis2 Timothy A. , Hartmann Constance B. , McCoy Kathleen L. 
Published: December 2022

AbstractGallium arsenide (GaAs) is a semiconductor utilized in the electronics industry. Chemical exposure of animals causes a local inflammatory reaction, but systemic immunosuppression. Mice were administered i.p. 200 mg/kg GaAs crystals or latex beads, or vehicle. Five days after exposure, splenic macrophages were defective, whereas thioglycolate-elicited peritoneal macrophages (PEC) were more efficient in processing the Ag, pigeon cytochrome c, than vehicle control macrophages. Various aspects of the MHC class II Ag-processing pathway were examined. Both macrophage populations normally presented a peptide fragment to the CD4+ T cells. Surface MHC class II expression on the PEC was up-regulated, but splenic cells had normal MHC class II expression. PEC had elevated levels of glutathione and cysteine, major physiologic reducing thiols. However, the cysteine content of splenic macrophages was diminished. Proteolytic activities of aspartyl cathepsin D, and thiol cathepsins B and L were decreased significantly in splenic macrophages. On the other hand, thiol cathepsin activities were increased selectively in PEC. Latex bead-exposed PEC were not more potent APC, and their thiol cathepsin activities were unchanged, indicating that phagocytosis and nonspecific irritation were not responsible. The phenotype of PEC directly exposed to GaAs mirrored cytokine-activated macrophages, in contrast to splenic macrophages from a distant site. Therefore, GaAs exposure differentially modulated cathepsin activities in splenic macrophages and PEC, which correlated with their Ag-processing efficiency. Perhaps such distinct alterations may contribute to the local inflammation and systemic immunotoxicity caused by chemical exposure.
Peripheral Immune Tolerance Blocks Clonal Expansion but Fails to Prevent the Differentiation of Th1 Cells
Authors: Malvey Erika-Nell , Jenkins Marc K. , Mueller Daniel L. 
Published: December 2022

AbstractClonal anergy in Ag-specific CD4+ T cells is shown in these experiments to inhibit IL-2 production and clonal expansion in vivo. We also demonstrate that the defect in IL-2 gene inducibility can be achieved in both naive and Th1-like memory T cells when repeatedly exposed to aqueous peptide Ag. Nevertheless, this induction of clonal anergy did not interfere with the capacity of naive T cells to differentiate into Th1-like effector cells, nor did it prevent such helper cells from participating in T-dependent IgG2a anti-hapten responses and delayed-type hypersensitivity reactions. Thus, clonal anergy can contribute to the development of Ag-specific immune tolerance by limiting the size of a Th cell population, but not by disrupting its effector function.
IL-18 Augments Perforin-Dependent Cytotoxicity of Liver NK-T Cells
Authors: Dao Tao , Mehal Wajahat Z. , Crispe I. Nicholas 
Published: December 2022

AbstractThe liver contains abundant cytotoxic cells, including NK-T cells, NK cells, and CTLs. However, the regulation of this cytotoxicity is not fully understood. In this study, we investigated the effect of a recently described cytokine, IL-18, which is present in large quantities in the liver, on the cytotoxicity of intrahepatic lymphocyte subpopulations. This effect of IL-18 was assessed by assaying the in vitro cytotoxicity of purified NK-T, NK, and T cells against a CD95- and perforin-sensitive T cell line, Jurkat. The results show that IL-18 enhances the killing activity of liver NK-T cells by a CD95-independent, perforin-dependent pathway. IL-18 also augments liver NK cell activity, but the exact mechanisms of this killing remain to be elucidated. Finally, the augmentation of the killing activities of liver NK-T and NK cells by IL-18 is not due to soluble TNF-α, because none of these cell populations had detectable TNF-α production.
Role of Conserved Glycosylation Site Unique to Murine Class I MHC in Recognition by Ly-49 NK Cell Receptor
Authors: Lian Rebecca H. , Freeman J. Douglas , Mager Dixie L. , Takei Fumio 
Published: December 2022

AbstractThe recognition of class I MHC molecules on target cells by the Ly-49 family of receptors regulates NK cytotoxicity. Previous studies have suggested that carbohydrates are involved in the recognition of class I MHC by Ly-49, although their precise role remains unclear. Here, we examined the role of asparagine-linked carbohydrates of the murine class I MHC in the binding to Ly-49A and Ly-49C. We have generated H-2Dd mutants that lack the highly conserved glycosylation sites at amino acid residues 86 in the α1 domain and 176 in the α2 domain, respectively. These mutant Dd cDNAs were transfected into leukemic cell lines, and the binding of the transfected cells to COS cells expressing Ly-49A or Ly-49C, as well as their susceptibility to lysis by Ly-49A+ NK cells, was examined. Only the mutation of the α2 domain glycosylation site significantly reduced the binding of Dd to Ly-49A and Ly-49C. Cells expressing Dd with the mutation at this site were partially resistant to killing by Ly-49A+ NK cells. These results suggest that, while carbohydrates linked to residue 176 seem to function as a part of the ligand structure for the Ly-49 family of NK receptors, there are additional structural features involved in this recognition. This glycosylation site is highly conserved among murine class I MHC but is not found among those of other species, suggesting that its role is unique to the murine immune system. It further suggests that murine class I MHC and Ly-49 gene families may have evolved in concert.
The Murine IL-13 Receptor α2: Molecular Cloning, Characterization, and Comparison with Murine IL-13 Receptor α1
Authors: Donaldson Debra D. , Whitters Matthew J. , Fitz Lori J. , Neben Tamlyn Yee , Finnerty Heather , Henderson Sheryl L. , O’Hara Richard M. , Beier David R. , Turner Katherine J. , Wood Clive R. , Collins Mary 
Published: December 2022

AbstractTwo components of a receptor complex for IL-13, the IL-4R and a low affinity IL-13-binding chain, IL-13Rα1, have been cloned in mice and humans. An additional high affinity binding chain for IL-13, IL-13Rα2, has been described in humans. We isolated a cDNA from the thymus that encodes the murine orthologue of the human IL-13Rα2. The predicted protein sequence of murine IL-13Rα2 (mIL-13Rα2) has 59% overall identity to human IL-13Rα2 and is closely related to the murine low affinity IL-13-binding subunit, IL-13Rα1. The genes for both mIL-13-binding chains map to the X chromosome. A specific interaction between mIL-13Rα2.Fc protein and IL-13 was demonstrated by surface plasmon resonance using a BIACORE instrument. Ba/F3 cells that were transfected with mIL-13Rα2 expressed 5000 molecules per cell and bound IL-13 with a single Kd of 0.5 to 1.2 nM. However, these cells did not proliferate in response to IL-13, and the IL-4 dose response was unaffected by high concentrations of IL-13. In contrast, the expression of mIL-13Rα1 by Ba/F3 cells resulted in a sensitive proliferative response to IL-13. Consistent with its lower affinity for IL-13, IL-13Rα1.Fc was 100-fold less effective than IL-13Rα2.Fc in neutralizing IL-13 in vitro. These results show that mIL-13Rα2 and mIL-13Rα1 are not functionally equivalent and predict distinct roles for each polypeptide in IL-13R complex formation and in the modulation of IL-13 signal transduction.
Protection from Lymphoma Cell Metastasis in ICAM-1 Mutant Mice: A Posthoming Event
Authors: Aoudjit Fawzi , Potworowski Edouard F. , Springer Timothy A. , St-Pierre Yves 
Published: December 2022

AbstractIt has been hypothesized that the intercellular adhesion receptors used by normal cells could also be operative in the spreading of circulating malignant cells to target organs. In the present work, we show that genetic ablation of the ICAM-1 gene confers resistance to T cell lymphoma metastasis. Following i.v. inoculation of LFA-1-expressing malignant T lymphoma cells, we found that ICAM-1-deficient mice were almost completely resistant to the development of lymphoid malignancy compared with wild-type control mice that developed lymphoid tumors in the kidneys, spleen, and liver. Histologic examinations confirmed that ICAM-1-deficient mice, in contrast to wild-type mice, had no evidence of lymphoid infiltration in these organs. The effect of ICAM-1 on T cell lymphoma metastasis was observed in two distinct strains of ICAM-1-deficient animals. Nonetheless, lymphoma cells migrated with the same efficiency to target organs in both normal and ICAM-1-deficient mice, indicating not only that ICAM-1 expression by the host is essential in lymphoma metastasis, but also that this is so at stages subsequent to homing and extravasation into target organs. These results point to posthoming events as a focus of future investigation on the control of metastasis mediated by ICAM-1.
Lung-Specific Transgenic Expression of KC Enhances Resistance toKlebsiella pneumoniaein Mice
Authors: Tsai Wan C. , Strieter Robert M. , Wilkowski Jodi M. , Bucknell Kathy A. , Burdick Marie D. , Lira Sergio A. , Standiford Theodore J. 
Published: December 2022

AbstractA vigorous host response is required to effectively clear pathogenic bacteria from the lungs and is dependent upon the recruitment and activation of neutrophils and macrophages. A family of chemotactic cytokines, referred to as chemokines, have been shown to participate in this complex protective response. In this study, we assessed the role of the C-X-C chemokine KC in lung antibacterial host defense using wild-type (wt) B6D2 mice or transgenic mice that had been bred on a B6D2 background expressing KC under the control of a Clara cell-specific promoter within the lung. The administration of Klebsiella pneumoniae to both wt and KC-transgenic mice resulted in a time-dependent expression of KC protein within the lung that peaked at 24 to 48 h postinoculation. When infected with K. pneumoniae, the KC-transgenic mice showed a striking improvement in survival compared with wt control mice. This improved survival was due to an increase in bacterial clearance, which occurred in association with a vigorous recruitment of neutrophils in the KC-transgenic mice compared with their wt control counterparts. No differences in the lung levels of the specific cytokines TNF-α, IFN-γ, IL-12, and IL-10 were noted. However, inducible macrophage inflammatory protein-2 levels were significantly decreased in the KC-transgenic mice compared with the wt mice. This study indicates that the compartmentalized overexpression of KC in vivo results in increased lung bacterial clearance and improved survival, which occurs in association with enhanced polymorphonuclear leukocyte influx to the lung.
IFN-γ Inhibits Activation-Induced Expression of E- and P-Selectin on Endothelial Cells
Authors: Melrose Jennifer , Tsurushita Naoya , Liu Gao , Berg Ellen L. 
Published: December 2022

AbstractE- and P-selectin are cell surface lectins that mediate leukocyte-endothelial cell adhesion and thereby participate in neutrophil recruitment into inflammatory sites. E-selectin can be induced on endothelial cells by various activators, including TNF-α, IL-1β, and PMA. Induction of E-selectin is blocked by pretreatment of endothelial cells with IL-4 or TGF-β, both of which have antiinflammatory properties in vivo. In addition to its well-known proinflammatory activities, IFN-γ also has antiinflammatory effects in vivo, one of which is inhibition of neutrophil recruitment. To determine whether IFN-γ inhibits neutrophil recruitment by inhibiting adhesion molecule expression, the effect of IFN-γ on activation-induced cell adhesion molecule expression by cultured HUVEC was evaluated. Pretreatment of endothelial cells with IFN-γ for 24 to 72 h before 6- to 24-h activation with IL-1β, TNF-α, or PMA resulted in significantly reduced levels of cell surface E-selectin, although levels of ICAM-1 and VCAM-1 were the same or increased. The reduction of cell surface E-selectin levels under these conditions was reflected in reduced levels of E-selectin mRNA, indicating an effect at the transcription level or RNA stability. Interestingly, the increase of cell surface P-selectin expression due to IL-4 treatment of HUVEC was also inhibited by IFN-γ, while constitutive levels of P-selectin were not. These results suggest that the inhibition of neutrophil recruitment by IFN-γ in vivo may be due, in part, to the ability of IFN-γ to inhibit E- and P-selectin up-regulation. Furthermore, these findings emphasize the process of leukocyte recruitment as an important step through which IFN-γ can direct the character of inflammatory reactions.
Subcellular Site of Expression and Route of Vaccination Influence Pulmonary Eosinophilia Following Respiratory Syncytial Virus Challenge in BALB/c Mice Sensitized to the Attachment G Protein
Authors: Bembridge Gary P. , Garcia-Beato Regina , López Juan A. , Melero Jose A. , Taylor Geraldine 
Published: December 2022

Abstract
The attachment glycoprotein (G) of respiratory syncytial virus (RSV) is synthesized as two mature forms: a membrane-anchored form and a smaller secreted form. Mutant cDNAs were constructed that encoded one or the other form of the protein and were expressed in recombinant vaccinia viruses (rVV). Mice were immunized with rVV by dermal scarification or i.p. injection to determine the contribution of the membrane-anchored and secreted forms of the G protein on the augmentation of pulmonary pathology seen following RSV challenge. Mice scarified with rVV expressing the membrane-anchored G protein had a markedly reduced pulmonary eosinophilic response following RSV challenge compared with mice scarified with rVV expressing either wild-type or secreted G protein. The induction of pulmonary eosinophilia in rVV-primed mice was also dependent upon the route of vaccination. An eosinophilic response was not observed in any groups of mice immunized i.p. with rVV expressing any of the different forms of the G protein The difference in pulmonary pathology observed between dermal scarification or i.p. vaccinated mice was not reflected in a difference in cytokine production by splenocytes from vaccinated and challenged mice restimulated with RSV in vitro. Both groups produced significant levels of IL-4 and IL-5. These data suggest that the local APCs and lymphoid environment, together with the form of the G protein, influence pulmonary pathology following RSV challenge.
Important Contributions of P-Selectin Glycoprotein Ligand-1-Mediated Secondary Capture to Human Monocyte Adhesion to P-Selectin, E-Selectin, and TNF-α-Activated Endothelium Under Flow In Vitro
Authors: Lim Yaw-Chyn , Snapp Karen , Kansas Geoffrey S. , Camphausen Raymond , Ding Han , Luscinskas Francis W. 
Published: December 2022

AbstractIn this study, an in vitro flow model and a blocking mAb to P-selectin glycoprotein ligand-1 (PSGL-1) were used to define the role of PSGL-1 in monocyte attachment and rolling on E- and P-selectin and in attachment and accumulation on 6-h TNF-α-activated HUVEC. KPL1, an adhesion-blocking mAb directed against the tyrosine sulfate motif of PSGL-1, abolished monocyte-adhesive interactions with P-selectin, but only partially blocked monocyte interaction with E-selectin. Further analysis showed that on E-selectin, KPL1 blocked only secondary (i.e., monocyte/monocyte) interactions, but did not block primary (i.e., monocyte/E-selectin) interactions, with secondary adhesion accounting for 90% of the total adhesive interactions on either E- or P-selectin. On cytokine-activated HUVEC, monocytes initially attached and formed linear strings of adherent cells, which involved both primary and secondary adhesion. PSGL-1 or L-selectin mAb reduced string formation, and the combination of PSGL-1 and L-selectin mAb prevented monocyte strings and inhibited 86% of accumulation. Monocyte attachment and rolling on purified adherent monocytes were also critically dependent on PSGL-1 on the adherent monocytes. These studies document that secondary interactions between monocytes, mediated by PSGL-1, are crucial for monocyte initial attachment, rolling, and accumulation on activated endothelium under laminar shear flow.
The Influence of Mast Cells on Pathways of Transepithelial Antigen Transport in Rat Intestine
Authors: Berin M. Cecilia , Kiliaan Amanda J. , Yang Ping-Chang , Groot Jack A. , Kitamura Yukihiko , Perdue Mary H. 
Published: December 2022

AbstractLuminal Ag challenge of intestinal segments from sensitized rats results in a rapid (∼3 min) secretory response. We previously showed in horseradish peroxidase (HRP)-sensitized rats that the initial phase of transepithelial Ag transport occurred via a transcellular route and was enhanced by sensitization. However, following the hypersensitivity reaction, Ag also crossed between epithelial cells. The aim of this study was to determine the role of mast cells in the altered transepithelial Ag transport. White spotting mast cell-deficient rats and +/+ littermate controls were sensitized to HRP. After 10 to 14 days, jejunal segments were resected, mounted in Ussing chambers, and challenged with HRP on the luminal side. Electron microscopy of jejunum fixed at 2 min showed a similarly enhanced endocytic transport of HRP in sensitized +/+ and Ws/Ws rats compared with naive controls. In sensitized +/+ rats, a secretory response occurred ∼3 min after challenge, and tissue conductance increased thereafter. Naive +/+ and sensitized Ws/Ws rats did not demonstrate a secretory response to HRP challenge, and conductance remained at baseline levels. The flux of HRP was elevated across tissue from sensitized +/+ rats but not across tissue from naive controls or sensitized Ws/Ws rats. The results indicate that sensitization enhances the initial phase of transepithelial uptake of Ag by transcytosis in a mast cell-independent manner. However, subsequent recruitment of the paracellular pathway for Ag transport in sensitized rats is dependent upon the presence of mast cells and occurs after the activation of such cells.
Expression and Functional Activity of the IL-8 Receptor Type CXCR1 and CXCR2 on Human Mast Cells
Authors: Lippert Undine , Artuc Metin , Grützkau Andreas , Möller Annelie , Kenderessy-Szabo Anna , Schadendorf Dirk , Norgauer Johannes , Hartmann Karin , Schweitzer-Stenner Reinhard , Zuberbier Thorsten , Henz Beate M. , Krüger-Krasagakes Sabine 
Published: December 2022

AbstractTo further elucidate mechanisms involved in mast cell accumulation at sites of cutaneous inflammation, we have studied the ability of human leukemic mast cells (HMC-1 cells) to express functionally active IL-8 receptors. Expression of mRNA for both types of IL-8 receptors (CXCR1 and CXCR2) was demonstrated by PCR and of both proteins by flow cytometry. Binding and competition studies with 125I-labeled IL-8 and its homologue melanoma growth stimulating activity (125I-labeled MGSA) revealed two specific binding sites for IL-8, K1 = 1.1 × 1011 M−1 and K2 = 5 × 107 M−1; and for MGSA, K1 = 2.8 × 1010 M−1 and K2 = 5 × 107 M−1. This finding was supported by a dose-dependent rise of cytosolic free calcium concentration ([Ca2+]i) induced by both chemokines and to a lesser extent by the homologue neutrophil-activating peptide-2 (NAP-2). A significant migratory response of human leukemic mast cells (HMC-1) was observed with all three chemokines at a range from 10−8 M to 10−9 M. Moreover, the formation of cellular F-actin was induced in a rapid, dose-dependent fashion, with a maximally 1.7-fold increase at 10−7 M. Using postembedding immunoelectron microscopy, we could show the expression of CXCR1 on the cytoplasmatic membrane of isolated human skin mast cells whereas CXCR2 was located in mast cell-specific granules. These findings demonstrate for the first time the functional expression of both types of IL-8 receptors on human mast cells, suggesting a role for their ligands during mast cell activation and recruitment.
Cutting Edge: Enhanced Anti-HIV-1 Activity and Altered Chemotactic Potency of NH2-Terminally Processed Macrophage-Derived Chemokine (MDC) Imply an Additional MDC Receptor
Authors: Struyf Sofie , Proost Paul , Sozzani Silvano , Mantovani Alberto , Wuyts Anja , De Clercq Erik , Schols Dominique , Van Damme Jo 
Published: December 2022

AbstractPosttranslational processing of chemokines increases (IL-8) or decreases (monocyte chemotactic protein-1) their chemotactic potency. Macrophage-derived chemokine (MDC) attracts monocytes, dendritic cells, activated lymphocytes, and NK cells and has reportedly anti-HIV-1 activity. Here we report that truncation of MDC by deletion of two NH2-terminal residues resulted in impaired binding to CC chemokine receptor (CCR)4, the only identified MDC receptor sofar. Truncated MDC(3-69) failed to desensitize calcium mobilization by MDC(1-69) or thymus- and activation-regulated chemokine (TARC), another CCR4 ligand. MDC(3-69) lacked HUT-78 T cell chemotactic activity but retained its capacity to attract monocytes and to desensitize chemotaxis. Compared with MDC(1-69), MDC(3-69) had weak but enhanced antiviral activity against M- and T-tropic HIV-1 strains. Furthermore, both MDC forms failed to signal through the orphan receptors Bonzo/STRL33 and BOB/GPR15 and to desensitize RANTES and stromal cell-derived factor (SDF)-1 responses in CCR5-transfected and CXC chemokine receptor (CXCR)4-transfected cells, respectively. These findings suggest that MDC recognizes another, yet unidentified, receptor. We conclude that minimal NH2-terminal truncation of MDC differentially affects its various immunologic functions.
IFN-α Is a Survival Factor for Human Myeloma Cells and Reduces Dexamethasone-Induced Apoptosis
Authors: Ferlin-Bezombes Martine , Jourdan Michel , Liautard Janny , Brochier Jean , Rossi Jean-François , Klein Bernard 
Published: December 2022

Abstract
IFN-α is used as a maintenance therapy in patients with multiple myeloma, but its benefit is a matter of controversy. In vitro studies show that IFN-α can both stimulate and inhibit myeloma cell proliferation. We have tested the effect of IFN-α on the survival of myeloma cell lines and primary plasma cells. IFN-α significantly reduced the apoptosis induced by removal of IL-6 in four IL-6-dependent myeloma cell lines. It also reduced the level of apoptosis induced by dexamethasone in these cell lines as well as in purified primary myeloma cells from seven patients. IFN-α promoted the survival of myeloma cells, which, following removal of IL-6, were blocked in G1 and died. However, unlike IL-6, IFN-α-treated cells remained mainly blocked in the G1 phase of the cycle. While the effects of IL-6 are mediated through stimulation of its gp130 receptor subunit, the IFN-α-induced survival of myeloma cells was independent of gp130 transducer activation (as demonstrated using a neutralizing anti-gp130 Ab). However, the signal transduction cascades activated by these two cytokines share at least some common elements, since stimulation with either IFN-α or IL-6 resulted in STAT3 phosphorylation. These results indicate that IFN-α promotes the survival, but not the proliferation, of myeloma cells, preventing the apoptosis induced by removal of IL-6 or addition of dexamethasone. This survival factor activity may explain the conflicting reports on the effects of IFN-α on myeloma cell proliferation.