bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon-γ receptor 2 expression as the deciding factor in human T, B, and myeloid cell proliferation or death
Authors: Bernabei Paola , Coccia Eliana M , Rigamonti Laura , Bosticardo Marita , Forni Guido , Pestka Sidney , Krause Christopher D , Battistini Angela , Novelli Francesco 
Published: September 2022

AbstractTheheterodimeric interferon (IFN)-γ receptor (IFN-γR) is formed of two chains. Here we show that the binding chain (IFN-γR1) was highly expressed on the membranes of T, B, and myeloid cells. Conversely, the transducing chain (IFN-γR2) was highly expressed on the surfaces of myeloid cells, moderately expressed on B cells, and poorly expressed on the surfaces of T cells. Differential cell membrane expression of IFN-γR2 determined the number of receptor complexes that transduced the IFN-γ signal and resulted in a different response to IFN-γ. After IFN-γ stimulation, high IFN-γR2 membrane expression induced rapid activation of signal transducer and activator of transcription-1 (STAT-1) and high levels of interferon regulatory factor-1 (IRF-1), which then triggered the apoptotic program. By contrast, low cell membrane expression resulted in slow activation of STAT-1, lower levels of IRF-1, and induction of proliferation. Because the forced expression of IFN-γR2 on T cells switched their response to IFN-γ from proliferative to apoptotic, we concluded that the surface expression of IFN-γR2 determines whether a cell stimulated by IFN-γ undergoes proliferation or apoptosis.
Identification of human CD93 as the phagocytic C1q receptor (C1qRp) by expression cloning
Authors: Steinberger Peter , Szekeres Andreas , Wille Stefan , Stöckl Johannes , Selenko Nicole , Prager Elisabeth , Staffler Günther , Madic Otto , Stockinger Hannes , Knapp Walter 
Published: September 2022

AbstractCD93 is a ∼120 kDa O-sialoglycoprotein that within the hematopoietic system is selectively expressed on cells of the myeloid lineage. So far, its primary structure and function were unknown. We used retroviral-expression cloning to isolate the CD93 cDNA. Sequence analysis revealed that CD93 is identical to a protein on human phagocytes termed C1q receptor (C1qRp). C1qRp was shown previously to mediate enhancement of phagocytosis in monocytes and was suggested to be a receptor of C1q and two other structurally related molecules. When studying CD93 transductants and control cells, we found that cells expressing CD93 have enhanced capacity to bind C1q. Furthermore, we show that immature dendritic cells (DC) express CD93/C1qRp, and mature DC, known to have reduced capacity for antigen uptake and to have lost the ability to phagocytose, show weak-to-negative CD93/C1qRp expression.
Potential role for Duffy antigen chemokine-binding protein in angiogenesis and maintenance of homeostasis in response to stress
Authors: Du Jianguo , Luan Jing , Liu Hua , Daniel Thomas O , Peiper Stephen , Chen Theresa S , Yu Yingchun , Horton Linda W , Nanney Lillian B , Strieter Robert M , Richmond Ann 
Published: September 2022

AbstractCXC chemokines, which induce angiogenesis, haveglutamine-leucine-arginine amino acid residues (ELR motif) in the aminoterminus and bind CXCR2 and the Duffy antigen chemokine-bindingprotein. Duffy, a seven transmembrane protein that binds CXC and CCchemokines, has not been shown to couple to trimeric G proteins or totransduce intracellular signals, although it is highly expressed on redblood cells, endothelial cells undergoing neovascularization, andneuronal cells. The binding of chemokines by Duffy could modulatechemokine responses positively or negatively. Positive regulation couldcome through the presentation of chemokine to functional receptors, andnegative regulation could come through Duffy competition withfunctional chemokine receptors for chemokine binding, thus serving as adecoy receptor. To determine whether Duffy has a role in angiogenesisand/or maintenance of homeostasis, we developed transgenic miceexpressing mDuffy under the control of the preproendothelinpromoter/enhancer (PPEP), which directs expression of the transgeneto the endothelium. Two PPEP-mDuffy-transgenic founders wereidentified, and expression of the transgene in the endothelium wasverified by Northern blot, RT-PCR, and immunostaining of tissues. Thephenotype of the mice carrying the transgene appeared normal by allvisual parameters. However, careful comparison of transgenic andnontransgenic mice revealed two phenotypic differences:mDuffy-transgenic mice exhibited a diminished angiogenic response to MIP-2 in the corneal micropocket assay, and mDuffy-transgenic miceexhibited enhanced hepatocellular toxicity and necrosis as comparedwith nontransgenic littermates in response to overdose of acetaminophen(APAP; 400 mg/kg body weight). Morover, APAP treatment was lethal in50% of the mDuffy-transgenic mice 24 h post challenge, and 100%of the nontransgenic littermates survived this treatment at the 24 h time point. Our data suggest that enhanced expression of mDuffy onendothelial cells can lead to impaired angiogenic response tochemokines and impaired maintenance of homeostasis in response to toxicstresses.
Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism
Authors: Wardrop S L , Wells C , Ravasi T , Hume D A , Richardson D R 
Published: September 2022

AbstractNramp2 is a widely expressed metal-ion transporter that is involved in dietary iron absorption in the duodenum and iron uptake from transferrin in peripheral tissues. Nramp1 is a related gene involved in regulation of host pathogen interaction. Nramp2 has at least two alternatively spliced isoforms, one of which contains an iron-responsive element in its 3′-untranslated region. In this study, we investigated the regulation of both isoforms of Nramp2 in activated primary macrophages from mouse strains with wild-type (Bcgr) or mutant (Bcgs) alleles. The Nramp2-IRE and/or -nonIRE transcripts were up-regulated in all mouse strains analyzed after treatment with interferon-γ and lipopolysaccharide. cDNA microarray analysis revealed that Nramp2 regulation is controlled discordantly from other iron-regulated genes and classical macrophage-activation genes in different mouse strains. We suggest that Nramp2 is regulated independently of known iron-responsive genes in macrophages, and its function in host defense is unrelated to Nramp1.
Role of chemokines in the biology of natural killer cells
Authors: Robertson Michael J 
Published: September 2022

AbstractNatural killer (NK) cells participate in innate and adaptive immuneresponses to obligate intracellular pathogens and malignant tumors. Twomajor NK cell subsets have been identified in humans:CD56dim CD16+ and CD56bright CD16−. RestingCD56dim CD16+ NK cells express CXCR1, CXCR2, CXCR3, CXCR4,and CX3CR1 but no detectable levels of CC chemokine receptors on thecell surface. They migrate vigorously in response to CXCL12 and CXC3L1. In contrast, resting CD56bright CD16− NK cells expresslittle CXCR1, CXCR2, and CXC3R1 but high levels of CCR5 and CCR7. Chemotaxis of CD56bright CD16− NK cells is stimulated mostpotently by CCL19, CCL21, CXCL10, CXCL11, and CXCL12. Followingactivation, NK cells can migrate in response to additional CC and CXCchemokines. Cytolytic activity of NK cells is augmented by CCL2, CCL3,CCL4, CCL5, CCL10, and CXC3L1. Moreover, proliferation of CD56dim CD16+ NK cells is costimulated by CCL19 and CCL21. Activated NK cells produce XCL1, CCL1, CCL3, CCL4, CCL5, CCL22, and CXCL8. Chemokines secreted by NK cells may recruit other effector cellsduring immune responses. Furthermore, CCL3, CCL4, and CCL5 produced byNK cells can inhibit in vitro replication of HIV. CCL3 and CXL10expression appear to be required for protective NK cell responses invivo to murine cytomegalovirus or Leishmania major,respectively. Moreover, NK cells participate in the in vivo rejectionof transduced tumor cells that produce CCL19 or CCL21. Thus, chemokinesappear to play an important role in afferent and efferent NK cellresponses to infected and neoplastic cells.
Monocyte cell adhesion induced by a human aminoacyl-tRNA synthetase-associated factor, p43: identification of the related adhesion molecules and signal pathways
Authors: Park Heonyong , Park Sang Gyu , Lee Joong-Won , Kim Taeho , Kim Gyuyoup , Ko Young-Gyu , Kim Sunghoon 
Published: September 2022

AbstractAn aminoacyl-tRNA synthetase-associated factor, p43, was recently shown to be secreted to induce a proinflammatory response. Because a proinflammatory response involves the cell-cell adhesion between endothelial and immune cells, we first examined the mechanism of p43-induced cell-cell adhesion of myelomonocytic leukemia cells. Intercellular adhesion molecule-1 (ICAM-1) was up-regulated by p43 and mediated p43-induced cell-cell adhesion via the interaction with LFA-1 or Mac-1. We also investigated p43-stimulated signaling pathways involved in the homotypic THP-1 cell adhesion. Because the specific inhibitors for PI3-K (phosphatidylinositol 3-kinase), ERK (extracellular signal-regulating kinase), and p38 MAPK (mitogen-activated protein kinase) blocked p43-stimulated ICAM-1 expression and homotypic THP-1 cell adhesion, these kinases were responsible for p43-induced cell-cell adhesion. p43-Dependent activation of ERK was inhibited by PI3-K inhibitors, and the activation of p38 MAPK was not. Thus, the results of this work suggest that p43 should induce cell-cell adhesion via the PI3-K/ERK- and p38 MAPK-dependent up-regulation of ICAM-1.
Reversible phosphatidylserine expression on blood granulocytes related to membrane perturbation but not DNA strand breaks
Authors: Yang Ming-Yu , Chuang Hau , Chen Rong-Fu , Yang Kuender D 
Published: September 2022

AbstractExposure of phosphatidylserine (PS) on the outer leaflet of the cell membrane is recognized as an early indicator of programmed cell death (apoptosis) in plant and mammalian cells. Currently, there is no literature describing that PS expression on the surface of white blood cells is reversible. We found that a hypotonic 0.2% NaCl or NH4Cl lysing solution used to separate white blood cells from red blood cells induced a reversible PS expression on the cell surface of granulocytes and monocytes but not lymphocytes. This reversible PS expression was associated with change of plasma membrane potential but not degranulation-associated membrane mobilization or DNA fragmentation. In contrast, TNF-α induced an irreversible PS expression, associated with apoptotic DNA fragmentation shown on gel electrophoresis. The fact that hypotonic shock induced a reversible PS expression on granulocytes, and TNF-α induced an irreversible PS expression associated with apoptotic DNA fragmentation indicate the new insight that expression of PS on the outer cell surface does not always represent cell apoptosis. Also, the reversible PS expression was associated with altered plasma-membrane potential but not DNA strand breaks, indicating that early PS expression may be related to the membrane perturbation but not directly related to DNA fragmentation in certain types of cells.
Activation of phagocytic cell NADPH oxidase by norfloxacin: a potential mechanism to explain its bactericidal action
Authors: El Bekay Rajaa , Álvarez Moisés , Carballo Modesto , Martín-Nieto José , Monteseirín Javier , Pintado Elizabeth , Bedoya Francisco J , Sobrino Francisco 
Published: September 2022

AbstractThe mechanisms underlying the bactericidal power of fluoroquinolones against intracellular parasites in host macrophages remain poorly understood. We have analyzed the effect of norfloxacin, a fluoroquinolone antibiotic, on the production of reactive oxygen intermediates (O2•− and H2O2) and NADPH oxidase activity in mouse macrophages. The generation of anion superoxide (O2•−) was found to be significantly greater in macrophages incubated with norfloxacin than in untreated controls. This enhancing effect of norfloxacin was dose-dependent and reached maximal values within 10 min after its addition. The O2•− generated was mainly intracellular, as determined by the use of specific dyes, such as lucigenin and luminol, and able to diffuse freely through the cell membrane. Also, the production of H2O2 was increased in macrophages in response to norfloxacin. The positive effect of norfloxacin was associated to an enhanced mobilization of NADPH oxidase subunits p47phox and p67phox from the cytosol to the plasma membrane in phagocytic cells. The effect of the antibiotic persisted in vivo for several hours. These data support the notion that norfloxacin inhibits mycobacterial growth within phagocytic cells by enhancing intracellular production of O2•− and other reactive oxygen species.
Toll-like receptor 9 mediates CpG-DNA signaling
Authors: Chuang Tsung-Hsien , Lee Jongdae , Kline Lois , Mathison John C , Ulevitch Richard J 
Published: September 2022

AbstractAmong the bacterial products known to activate the innate immune ‘1system is bacterial DNA. This activity resides within the nonmethylated CpG motifs of the DNA and is recapitulated using appropriate synthetic CpG containing oligodeoxynucleotides (CpG-ODN). TLR9-deficient mice were shown to exhibit a nonresponsive phenotype-to-bacterial DNA and CpG-ODN. Here, we describe a model system to further characterize CpG-ODN and TLR9 interactions using ectopically expressed TLR9 in HEK293 cells. Expression of TLR9 confers cellular responsiveness to CpG-ODN but not to the other bacterial products. Previous studies identified species-specific CpG-containing sequences; here, we show that expression of murine TLR9 favors responses to CpG-ODN motifs specific to mouse cells, and expression of human TLR9 favors CpG-ODN known to preferentially activate human cells. Response patterns to various CpG-ODN motifs were parallel when cells containing an ectopically expressed TLR9 and endogenous receptor were compared. Here, we also show that TLR9 acts at the cell surface and engages an intracellular signaling pathway that includes MyD88, IRAK, and TRAF6.
Capacitative Ca2+ influx and activation of the neutrophil respiratory burst. Different regulation of plasma membrane- and granule-localized NADPH-oxidase
Authors: Granfeldt Daniel , Samuelsson Marie , Karlsson Anna 
Published: September 2022

AbstractThe neutrophil NADPH-oxidase may be activated in the plasma membrane, resulting in release of oxygen metabolites extracellularly, or in the granule or phagosomal membranes, giving intracellular production of oxidants. An increase in [Ca2+]i mediated through binding of fMLF to its receptor is part of a signaling cascade that activates the plasma membrane-localized oxidase. In contrast, a rise in [Ca2+]i induced by a Ca2+ ionophore results in activation of the intracellular pool of oxidase. We mimicked fMLF-induced emptying of intracellular Ca2+ stores with thapsigargin. This induced a pronounced intracellular oxidase activity but no extracellular release of oxidants. The thapsigargin-induced effect was dependent on capacitative Ca2+ influx, because the effect was inhibited dose-dependently by EGTA and the Ca2+ channel blocker La3+. At La3+ concentrations between 200 and 400 μM, thapsigargin also induced a massive extracellular production of superoxide anion. No other channel blockers tested induced a similar effect. We conclude that elevation in [Ca2+]i by capacitative Ca2+ influx induces NADPH-oxidase activation at an intracellular site. Further, activation of the plasma membrane-localized NADPH-oxidase is regulated by a more complex Ca2+ signaling, involving capacitative Ca2+ influx and possibly the specific action of La3+-sensitive Ca2+ channels.
Activation of macrophages by gliadin fragments: isolation and characterization of active peptide
Authors: Tučková Ludmila , Novotná Jana , Novák Petr , Flegelová Zuzana , Květoň Tomáš , Jelínková Lenka , Zídek Zdeněk , Man Petr , Tlaskalová-Hogenová Helena 
Published: September 2022

AbstractCeliac disease, induced by dietary gluten, is characterized by mucosal atrophy and local inflammation associated with cell infiltration and activation. Unlike other food proteins, gluten and its proteolytic fragments, besides inducing a specific immune response, were shown to activate components of innate immunity and cause, e.g., direct stimulation of TNF-α and IL-10 and a significant rise in NO production by peritoneal macrophages. The identity of the active fragments was established by separating the peptic digest of gliadin by RP-HPLC chromatography. The purest fraction with the highest activity was analyzed by mass spectrometry, and the gliadin peptide sequence was identified as VSFQQPQQQYPSSQ. This peptide (T) and its N- and C-terminally shortened forms (A, B, C and D, E, F) were synthesized. Peptide B (FQQPQQQYPSSQ) elicited the highest TNF-α, IL-10, and RANTES secretion and increase in IFN-γ-primed NO production by mouse macrophages. In contrast, C-terminally shortened peptides had a lower ability to stimulate macrophages than the native form.
T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor
Authors: Monaco Claudia , Andreakos Evangelos , Young Sylvia , Feldmann Marc , Paleolog Ewa 
Published: September 2022

AbstractAdhesion of leukocytes to the vascular endothelium is an early event in inflammation. Since cell-cell signaling may be an important stimulus for endothelial activation, we focused in this study on the role of contact-mediated activation by T lymphocytes of endothelial cells (EC). T lymphocytes were cultured with anti-CD3 monoclonal antibody or in the presence of a combination of TNF-α, interleukin (IL)-6, and IL-2, prior to fixation and coculture with human umbilical vein EC. Fixed, activated (anti-CD3- or cytokine-stimulated), but not unstimulated T cells, induced release of monocyte chemotactic protein-1, IL-8, and IL-6 by EC in a contact-dependent manner. Moreover, expression of tissue-factor antigen and activity was also significantly increased. Addition of anti-CD40 ligand antibody abolished T cell-induced activation of EC. Our data suggest that contact-mediated activation of EC by T cells, involving ligand:counter ligand interactions such as CD40:CD40 ligand, may represent a novel pathogenic mechanism of progression in inflammatory diseases such as atherosclerosis or rheumatoid arthritis.
Endothelins regulate mediator production of rat tissue-cultured mucosal mast cells. Up-regulation of Th1 and inhibition of Th2 cytokines
Authors: Coulombe Martin , Battistini Bruno , Stankova Jana , Pouliot Philippe , Bissonnette Elyse Y 
Published: September 2022

AbstractMast cells have been shown to produce endothelin-1 (ET-1) and to express ET receptors. Thus, we postulated that ETs modulate mast cell mediator production in an autocrine manner. Rat tissue-cultured mast cells (RCMC-1) were incubated with exogenous ET-1 or ET-3, and β-hexosaminidase release and TNF, IL-4, IL-10, IL-12, IL-13, macrophage inflammatory protein-1α (MIP-1α), and nitric oxide (NO) production were investigated. ET-1 and -3 induced the release of β-hexosaminidase and TNF and of mRNA expression. An antagonist of the ETB receptor subtype abrogated ET-stimulated TNF release, although ETA and ETB receptors have been identified by immunocytochemistry. It is interesting that ET-1 and ET-3 inhibited (25–30%) mRNA expression of Th2-type cytokines (IL-4, IL-10, and IL-13) and increased IL-12 release (39% and 41%, respectively) without affecting MIP-1α and NO production. Thus, our data suggest that ETs may play an important role in modulating the cytokine network by regulating Th1/Th2 cytokine production by mast cells.
Flt-3 ligand (FL) drives differentiation of rat bone marrow-derived dendritic cells expressing OX62 and/or CD161 (NKR-P1)
Authors: Brissette-Storkus Cynthia S , Kettel J C , Whitham T F , Giezeman-Smits K M , Villa L A , Potter D M , Chambers William H 
Published: September 2022

AbstractBone marrow-derived dendritic cells (DC) of the rat have not been as well characterized as those from the mouse. Here, large quantities of bone marrow-derived rat DC were generated when Flt-3 ligand (FL) was used as an adjunct to granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). These cells displayed a typical DC phenotype, expressing MHC class II, CD54, CD80, CD86, and CD11b/c. These DC also uniformly expressed low levels of CD161 and expressed OX62 in a bimodal distribution. Few cells were recovered from cultures grown without FL, and they failed to express OX62 or CD161. The DC generated with FL were more potent antigen-presenting cells in mixed lymphocyte cultures than cells grown without FL, and among FL-derived cells, the OX62+ cells were slightly more stimulatory than OX62− cells. Thus, FL is a useful cytokine for obtaining large quantities of functional rat DC subsets in vitro.
Bone marrow CD34+ progenitor cells stimulated with stem cell factor and GM-CSF have the capacity to activate IgD− B cells through direct cellular interaction
Authors: Hirohata Shunsei , Yanagida Tamiko , Tomita Tetsuya , Yoshikawa Hideki , Ochi Takahiro 
Published: September 2022

AbstractRecent studies have suggested the involvement of bone marrow in the pathogenesis of rheumatoid arthritis (RA), in which proliferation of monocyte-lineage cells (MLC) as well as local B cell activation in the synovium play an important role. Here, we show that bone marrow-derived MLC have the capacity to activate human peripheral blood IgD− B cells. Bone marrow CD34+ cells from RA patients that had been stimulated with stem cell factor and GM-CSF for 3–4 weeks (&gt;90% CD14+ HLA-DR+ cells, &lt;0.5% CD19+ B cells, and &lt;0.5% CD3+ T cells; MLC) induced the production of IgG much more effectively than that of IgM by highly purified B cells from healthy donors in the presence of IL-2 and IL-10. CD34+ cells from cord blood or from bone marrow of osteoarthritis patients also displayed the capacity to induce IgG production. The induction of IgG production by the bone marrow-derived MLC was markedly decreased when they were separated from B cells by a membrane filter. The bone marrow-derived MLC interacted preferentially with IgD− B cells to induce IgG production. These results indicate that upon stimulation with stem cell factor and GM-CSF, CD34+ progenitor cells differentiate into MLC that activate preferentially IgD− B cells through direct cellular interactions to produce IgG. Therefore, the data suggest that the accelerated recruitment of MLC from the bone marrow to the synovium might play a role in the local B cell activation in RA.
Human neutrophil defensins induce lung epithelial cell proliferation in vitro
Authors: Aarbiou Jamil , Ertmann Marloes , van Wetering Sandra , van Noort Peter , Rook Denise , Rabe Klaus F , Litvinov Sergey V , van Krieken J Han J M , de Boer Willem I , Hiemstra Pieter S 
Published: September 2022

AbstractRepair of injured airway epithelium is often accompanied by an influx of leukocytes, and these cells have been suggested to contribute to the repair process. The aim of the present study was to investigate the effect of neutrophil defensins—antimicrobial peptides present in large amounts in the neutrophil— on proliferation of cultured lung epithelial cells. Neutrophil defensins at 4–10 μg/ml enhanced proliferation of the A549 lung epithelial cell line as assessed using cell counting, BrdU incorporation, and the tetrazolium salt MTT assay. Higher, cytotoxic concentrations of defensins decreased cell proliferation. Whereas defensin-induced cell proliferation was not inhibited by the EGF receptor tyrosine kinase inhibitor AG1478, it was completely inhibited by the mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor U0126, suggesting that defensins mediate cell proliferation via an EGF receptor-independent, MAP kinase signaling pathway. Although the cytotoxic effect of defensins was inhibited by α1-proteinase inhibitor, the defensin-induced cell proliferation was not affected. These data suggest that neutrophil defensins may possibly be involved in epithelial repair in the airways by inducing lung epithelial cell proliferation.