bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of interleukin-8 gene expression after phagocytosis of zymosan by human monocytic cells
Authors: Friedland Jon S , Constantin Despina , Shaw Terry C , Stylianou Eleni 
Published: September 2022

AbstractMonocyte phagocytosis of pathogens or inflammatory debris leads to chemokine secretion and heralds the influx of leukocytes to the site of injury. Persistent chemokine secretion can lead to tissue damage. However, the mechanisms by which phagocytosis regulates chemokine synthesis remain poorly understood. As a first step, we have studied regulation of interleukin (IL) 8 gene expression after interaction with zymosan or latex. IL-8 secretion was consistently one- or twofold higher after incubation with zymosan than with latex. Nuclear factor (NF) κB translocation to the nucleus was induced by zymosan but not latex, indicating that its translocation is dependent on the nature of the phagocytic stimulus. NFκB activation coincided with IκBα degradation but had no effect on processing of NFκB1/p105, the precursor of the NFκB protein p50. The NFκB inhibitor gliotoxin abrogated zymosan-induced IL-8 synthesis in peripheral blood monocytes, further demonstrating that the induction of IL-8 mRNA by zymosan is NFκB dependent. SB203580 inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway significantly decreased zymosan-induced IL-8 mRNA accumulation. Inhibitors of protein kinases A and C or tyrosine kinases had no significant effect on zymosan-induced IL-8 synthesis. These data indicate that p38 MAPK and NFκB are critical in controlling zymosan-induced IL-8 secretion.
Morphine modulates lymph node-derived T lymphocyte function: role of caspase-3, -8, and nitric oxide
Authors: Wang Jinghua , Charboneau Richard , Balasubramanian Sudha , Barke Roderick A , Loh Horace H , Roy Sabita 
Published: September 2022

AbstractThe major objective of this paper is to characterize the mechanism by which morphine modulates lymphocyte function and if these effects are mediated through the μ-opioid receptor. We evaluated the in vitro effects of morphine on lymphocytes that were freshly isolated from lymph nodes from wild type (WT) and μ-opioid receptor knock-out (MORKO) mice. Results show that morphine inhibits Con A-induced lymph node T-cell proliferation and IL-2 and IFN-γ synthesis in a dose-dependent manner. This effect was abolished in lymph node cells isolated from MORKO mice. The inhibition of T-cell function with low-dose morphine was associated with an increase in caspase-3- and caspase-8-mediated apoptosis. The inhibition of T-cell function with high-dose morphine was associated with an increase in the inducible NO synthase mRNA expression. NG-nitro-L-arginine methyl ester (l-NAME) antagonized the apoptosis induced by high-dose morphine. Our results suggest that low-dose morphine, through the μ-opioid receptor, can induce lymph node lymphocyte apoptosis through the cleavage activity of caspase-3 and caspase-8. Morphine at high doses induces NO release. This effect of morphine is also mediated through the μ-opioid receptor present on the surface of macrophages.
Inhibition of antibody-dependent stimulation of lipoteichoic acid-treated human monocytes and macrophages by polyglycerolphosphate-reactive peptides
Authors: Gargir Ari , Ofek Itzhak , Hasty David , Meron-Sudai Shiri , Tsubery Hayim , Keisari Yona , Nissim Ahuva 
Published: September 2022

AbstractBy itself, lipoteichoic acid (LTA) obtained from S. pyogenes, S. aureus, or E. hirae poorly stimulated cytokine production by macrophages, whereas in the presence of anti-polyglycerol phosphate (PGP), the cells secreted significant amounts of IL-6. Two peptides constructed from the deduced sequence of the selected anti-PGP phage-antibody's complementary-determining region 3 of the variable heavy chain (VH-CDR3) reacted specifically with PGP. The monomeric form of the peptides markedly inhibited cytokine production by macrophages pretreated with LTA and anti-LTA. In contrast, the polyvalent form of biotinylated peptides complex with streptavidin-induced cytokine production by the LTA-treated macrophages. The data taken together support the concept that cross-linking of macrophage-bound LTA by anti-PGP is required for cytokine release by these cells. Importantly, these studies identified small, PGP-reactive peptides as potential tools in reducing this proinflammatory process.
CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis
Authors: Pardo Annie , Smith Kathleen M , Abrams John , Coffman Robert , Bustos Martha , McClanahan Terrill K , Grein Jeffrey , Murphy Erin E , Zlotnik Albert , Selman Moisés 
Published: September 2022

AbstractHypersensitivity pneumonitis (HP) is a lung inflammatory disorder characterized by accumulation of T lymphocytes. However, the mechanisms implicated in this process remain undefined. We examined the expression of dendritic cell (DC)-derived CC chemokine 1 (CK1)/CCL18, a chemokine putatively involved in naive T cell recruitment, in lungs from 10 patients with HP, 9 patients with idiopathic pulmonary fibrosis (IPF), and 20 healthy lungs. CCL18 was measured by real-time quantitative PCR and localized in lungs by in situ hybridization and immunohistochemistry. CCL18 expression was significantly increased in lungs affected by HP in comparison with lungs affected by IPF (2,085±393 vs. 1,023±110; P&lt;0.05) and controls (2,085±393 vs. 467±94; P&lt;0.01). Macrophages, DCs, and alveolar epithelial cells were the main sources of CCL18. There was a direct correlation between the levels of tissue CCL18 and the number of lymphocytes in the bronchoalveolar lavage fluids. High levels of CCL18 were detected in the subacute rather than the chronic phase of HP. These findings suggest a role for CCL18 in the pathogenesis of HP.
CD antigens 2001
Authors: Mason David , André Pascale , Bensussan Armand , Buckley Chris , Civin Curt , Clark Edward , de Haas Masja , Goyert Sanna , Hadam Martin , Hart Derek , Horejší Václav , Meuer Stefan , Morrissey James , Schwartz-Albiez Reinhard , Shaw Stephen , Simmons David , Uguccioni Mariagrazia , van der Schoot Ellen , Vivier Eric , Zola Heddy 
Published: September 2022

AbstractThis paper reviews the Seventh Human Leucocyte Differentiation Antigen (HLDA7) workshop. Due to the limitations of “blind” antibody screening, which had been evident at the previous meeting in 1996, participants at HLDA7 adopted a more selective approach to the choice of antibodies by identifying new CD specificities. This resulted in the addition of more than 80 new CD specificities. Plans for the eighth and subsequent workshops are also previewed.
Involvement of caspases and of mitochondria in Fas ligation-induced eosinophil apoptosis: modulation by interleukin-5 and interferon-γ
Authors: Létuvé Séverine , Druilhe Anne , Grandsaigne Martine , Aubier Michel , Pretolani Marina 
Published: September 2022

AbstractIn this study, we examined the relative importance of caspases and mitochondria in Fas-mediated eosinophil apoptosis. Stimulation of human peripheral blood eosinophils with an agonistic anti-human Fas monoclonal antibody, but not with control IgM, induced a time-dependent increase in their apoptosis, which was associated with a loss in mitochondrial transmembrane potential (ΔΨm) and with caspase-8 and caspase-3 activation. Interleukin (IL)-5 and interferon (IFN)-γ, two cytokines known to prolong eosinophil survival, inhibited Fas-mediated apoptosis and caspase activation but poorly affected the decrease in ΔΨm. Eosinophil incubation with bongkrekic acid, an inhibitor of the mitochondrial permeability transition pore (MPTP) opening, failed to modify Fas-mediated loss in ΔΨm, caspase activation, and apoptosis. In contrast, caspase inhibitors markedly reduced eosinophil apoptosis without significantly affecting ΔΨm dissipation. We conclude that caspase-8 and caspase-3 activation, but not MPTP opening, mediate Fas-induced eosinophil apoptosis and are the main targets for the protective effect of IL-5 and IFN-γ.
Intercellular cell adhesion molecule-1 regulates lymphocyte movement into intestinal microlymphatics of rat Peyer's patches
Authors: Hokari Ryota , Miura Soichiro , Nagata Hiroshi , Fujimori Hitoshi , Koseki Seiichiro , Kato Shingo , Kurose Iwao , Sekizuka Eiichi , Granger D Neil , Ishii Hiromasa 
Published: September 2022

AbstractThe objective of this study was to determine whether specific adhesion molecules modulate lymphocyte movement from Peyer's patches into intestinal microlymphatics. The fluorochrome acridine orange was injected via a micropipette into Peyer's patches to fill lymphatics. The flux of labeled lymphocytes into intestinal microlymphatics was monitored with intravital fluorescence microscopy. The lymphatic microvessels in the perifollicular area of Peyer's patches were filled with lymphocytes, most of which remained within the lymphatics. Some lymphocytes became detached and were drained into intestinal lymph. Administration of antibodies directed against ICAM-1 significantly increased lymphocyte flux into interfollicular lymphatics. The immunohistochemical study showed intense ICAM-1 expression on the lymphocytes densely packed in the lymphatics surrounding follicles in Peyer's patches. A large number of lymphocytes are normally sequestered in the lymphatic network of Peyer's patches. This sequestration of lymphocytes is largely mediated by ICAM-1-dependent cell-cell interactions.
Cytokines regulate membrane adenosine deaminase on human activated lymphocytes
Authors: Cordero Oscar J , Salgado Francisco J , Fernández-Alonso Carmen M , Herrera Carolina , Lluis Carmen , Franco Rafael , Nogueira Montserrat 
Published: September 2022

AbstractCD26 is a lymphocyte marker that can anchor adenosine deaminase (ADA) on the T cell surface. We found that ADA is regulated by cytokines on the cell surface during T cell activation. By means of flow cytometry, immunofluorescence, and immunoblotting techniques, we found that interleukin (IL)-2 and IL-12 up-regulate ecto-ADA and CD26 expression. In clear contrast, IL-4 led to down-regulation of lymphocyte surface ADA without modifying the level of CD26. Moreover, neither circulating ADA transcription nor mRNA translation was regulated by cytokines. These results, along with absence of total-ADA modulation, the variable amount of ADA found in purified plasma membranes, and the different effect of Brefeldin A on the surface presence of ADA and CD26 indicated that cytokines regulate the translocation of ADA towards the cell surface through a mechanism not involving CD26. Ecto-ADA protected activated lymphocytes from the toxic effects of extracellular adenosine. Therefore, this cell surface ADA control might constitute part of the fine immunoregulatory mechanism of adenosine-mediated signaling through purinergic receptors in leukocytes.
Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants
Authors: Weinberger Barry , Laskin Debra L , Mariano Thomas M , Sunil Vasanthi R , DeCoste Christina J , Heck Diane E , Gardner Carol R , Laskin Jeffrey D 
Published: September 2022

AbstractPotential mechanisms underlying impaired chemotactic responsiveness of neonatal neutrophils were investigated. Two distinct chemoattractants were compared: bacterially derivedN-formyl-methionyl-leucyl-phenylalanine (fMLP) and a unique chemotactic monoclonal antibody, designated DL1.2, which binds to a neutrophil antigen with an apparent molecular mass of 120 kDa. Chemotaxis of neutrophils toward fMLP, as well as DL1.2, was reduced in neonates when compared with adult cells. This did not appear to be a result of decreased fMLP receptor or DL1.2 antigen expression by neonatal neutrophils. fMLP, but not DL1.2, induced a rapid increase in intracellular calcium in adult and neonatal cells, which reached a maximum within 30 s. The calcium response of cells from neonates to fMLP was reduced when compared with adult cells, and an unresponsive subpopulation of neonatal neutrophils was identified. NF-κB nuclear binding activity induced by fMLP and DL1.2, as well as expression of the p65 NF-κB subunit and IκB-α, was also significantly reduced in neonatal cells, when compared with adult cells. In contrast, although fMLP, but not DL1.2, activated p42/44 and p38 mitogen-activated protein (MAP) kinases in neutrophils, no differences were observed between adults and neonates. Chemotaxis of adult and neonatal neutrophils toward fMLP and DL1.2 was also blocked to a similar extent by inhibitors of phosphatidylinositol 3-kinase, as well as an inhibitor of NF-κB. These findings indicate that reduced chemotactic responsiveness in neonatal neutrophils is a result of, at least in part, aberrations in chemoattractant-induced signaling. However, the biochemical pathways mediating this defect appear to be related to the specific chemoattractant.
Nutrients and their role in host resistance to infection
Authors: Field Catherine J , Johnson Ian R , Schley Patricia D 
Published: September 2022

AbstractAlmost all nutrients in the diet play a crucial role in maintaining an “optimal” immune response, such that deficient and excessive intakes can have negative consequences on immune status and susceptibility to a variety of pathogens. Iron and vitamin A deficiencies and protein-energy malnutrition are highly prevalent worldwide and are important to the public health in terms of immunocompetence. There are also nutrients (i.e., glutamine, arginine, fatty acids, vitamin E) that provide additional benefits to immunocompromised persons or patients who suffer from various infections. The remarkable advances in immunology of recent decades have provided insights into the mechanisms responsible for the effects of various nutrients in the diet on specific functions in immune cells. In this review, we will present evidence and proposed mechanisms for the importance of a small group of nutrients that have been demonstrated to affect host resistance to infection will be presented. An inadequate status of some of these nutrients occurs in many populations in the world (i.e., vitamin A, iron, and zinc) where infectious disease is a major health concern. We will also review nutrients that may specifically modulate host defense to infectious pathogens (long-chain polyunsaturated n-3 fatty acids, vitamin E, vitamin C, selenium, and nucleotides). A detailed review of the effect of long-chain polyunsaturated n-3 fatty acids on host defense is provided as an example of how the disciplines of nutrition and immunology have been combined to identify key mechanisms and propose nutrient-directed management of immune-related syndromes.
Neutrophil leukocyte motility requires directed water influx
Authors: Loitto Vesa-Matti , Forslund Tony , Sundqvist Tommy , Magnusson Karl-Eric , Gustafsson Mikael 
Published: September 2022

AbstractThe ability of neutrophils to sense and move to sites of infection is essential for our defense against pathogens. For motility, lamellipodium extension and stabilization are prerequisites, but how cells form such membrane protrusions is still obscure. Using contrast-enhanced video microscopy and Transwell® assays, we show that water-selective aquaporin channels regulate lamellipodium formation and neutrophil motility. Addition of anti-aquaporin-9 antibodies, HgCl2, or tetraethyl ammonium inhibited the function(s) of the channels and blocked motility-related shape changes. On human neutrophils, aquaporin-9 preferentially localized to the cell edges, where N-formyl peptide receptors also accumulated, as assessed with fluorescence microscopy. To directly visualize water fluxes at cell edges, cells were loaded with high dilution-sensitive, self-quenching concentrations of fluorophore. In these cells, motile regions always displayed increased fluorescence compared with perinuclear regions. Our observations provide the first experimental support for motility models where water fluxes play a pivotal role in cell-volume increases accompanying membrane extensions.
fMLP-induced in vitro nitric oxide production and its regulation in murine peritoneal macrophages
Authors: Sodhi Ajit , Biswas Subhra K 
Published: September 2022

AbstractBacterial N-formyl peptides such asN-formyl-methionyl-leucyl-phenylalanine (fMLP) are important mediators of monocyte/macrophage recruitment and activation at the sites of inflammation. In the current study, the role of nitric oxide (NO) in the activation of murine peritoneal macrophages to tumoricidal state in response to in vitro fMLP treatment has been investigated. Murine peritoneal macrophages on treatment with fMLP showed a dose- and time-dependent production of NO together with increased tumoricidal activity against P815 mastocytoma cells. L-NMMA, a specific inhibitor of L-arginine pathway, inhibited the fMLP-induced NO secretion and macrophage-mediated tumoricidal activity against P815 cells. These results indicate the L-arginine-dependent production of NO to be one of the effector mechanisms contributing to the tumoricidal activity of fMLP-treated macrophages. The expression of iNOS protein and iNOS mRNA is also observed. The pharmacological inhibitors genistein, wortmannin, H7, PD98059, TPCK, and pertussis toxin (PTX) blocked the fMLP-induced NO production, suggesting the involvement of tyrosine kinases, PI3K, PKC, p42/44 MAPkinase, NF-κB, and G-proteins. The expression of phospho-p42/44 MAPK and phospho-IκB was also observed. The role of protein phosphatases in the above pathway has been suggested using the specific inhibitors of these phosphatases, i.e., okadaic acid and sodium orthovanadate.
Cyclosporin A inhibition of macrophage colony-stimulating factor (M-CSF) production by activated human T lymphocytes
Authors: Frétier Stéphanie , Besse Arnaud , Delwail Adriana , Garcia Martine , Morel Franck , Leprivey-Lorgeot Valérie , Wijdenes John , Praloran Vincent , Lecron Jean-Claude 
Published: September 2022

AbstractM-CSF is a pleiotropic cytokine involved in the survival, proliferation, and differentiation of cells of the monocyte/macrophagelineage. M-CSF is produced by numerous cells including CD3-activated Tcells. M-CSF serum levels are increased during acute graft rejection. We tested the in vitro production of M-CSF, GM-CSF, IL-2, and IL-4 byT-cell clones costimulated by CD3 and accessory activation pathways and the effects of cyclosporin A and methylprednisolone. The nine clonesstudied and CD4+ cells purified from peripheral bloodmononuclear cells (PBMC) spontaneously produced low levels of M-CSF, which PMA and CD3 mAb strongly enhanced. In contrast to IL-2, CD28 mAbdid not further enhance this production. CsA inhibited M-CSF productionby clones and purified CD4 T cells. Addition of IL-2, anti IL-2, oranti CD25 mAb to the cultures demonstrated that CsA down-regulatedM-CSF synthesis by activated T cells through its inhibition of IL-2synthesis. These results could help to better understand the complexmechanisms of acute graft rejection and immunosuppression.
Cytokine-mediated regulation of CXCR4 expression in human neutrophils
Authors: Nagase Hiroyuki , Miyamasu Misato , Yamaguchi Masao , Imanishi Masako , Tsuno Nelson H , Matsushima Kouji , Yamamoto Kazuhiko , Morita Yutaka , Hirai Koichi 
Published: September 2022

AbstractSeveral lines of evidence have suggested that a CXC chemokine receptor 4 (CXCR4)/stromal cell-derived factor-1 [SDF-1; CXC chemokine ligand 12 (CXCL12)] pair is involved in baseline trafficking of leukocytes into extravascular tissues and that modulation of surface CXCR4 expression may represent an alternative mechanism for control of cell-specific biological responses to SDF-1/CXCL12. We explored the regulation of CXCR4 expression by cytokines in polymorphonuclear neutrophils (PMNs). No significant surface expression of CXCR4 in freshly isolated PMNs was detected, but expression became apparent gradually during incubation. SDF-1α/CXCL12 initiated Ca2+ mobilization and migratory responses in 20 h cultured PMNs. The surface CXCR4 expression was suppressed most potently by interferon-γ (IFN-γ). IFN-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF also inhibited spontaneous CXCR4 expression. Real-time, quantitative PCR experiments revealed that a spontaneous increase and an IFN-γ-mediated decrease in surface CXCR4 paralleled changes in the CXCR4 mRNA level. These results on PMNs support the argument that the SDF-1 (CXCL12)/CXCR4 system is regulated by cell type-specific mechanisms.
Fas activation opposes PMA-stimulated changes in the localization of PKCδ: a mechanism for reducing neutrophil adhesion to endothelial cells
Authors: Hendey Bill , Zhu Chun Liu , Greenstein Stephanie 
Published: September 2022

AbstractWe have shown previously that Fas activation results in a partial reduction of phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophil adhesion to endothelial cells. The reduction in adhesion precedes early membrane markers of apoptosis and is not associated with any loss of membrane integrity. Rather, Fas activation reduces the PMA-stimulated expression and aggregation of β2 integrins responsible for endothelial adhesion. A possible signaling mechanism for Fas effects on adhesion is the localization of protein kinase C δ (PKCδ). Western blot and immunofluorescence studies indicated that 1 h of Fas activation is required to reduce PMA-stimulated translocation of PKCδ to the membrane and adhesion. Rottlerin, a PKCδ inhibitor, also reduced PMA-induced PKCδ translocation and adhesion. In contrast, Gö6976, an inhibitor of conventional PKC isotypes, did not affect PMA-stimulated PKCδ translocation or reduce adhesion. There was no additive effect of Fas activation and rottlerin on reducing adhesion, suggesting that both agents were using a common pathway.
Chemotactic activity of human blood leukocytes in plasma treated with EDTA: chemoattraction of neutrophils about monocytes is mediated by the generation of NAP-2
Authors: Malawista Stephen E , Van Damme Jo , Smallwood Joan I , de Boisfleury Chevance Anne 
Published: September 2022

AbstractIn slide preparations of human blood leukocytes in autologous plasma containing EDTA, many adherent monocytes are initially chemotactic for neutrophils (PMN). We have identified the chemotactic factor that they generate as neutrophil-activating peptide-2 (NAP-2), as evidenced by distraction of the gradient by authentic human NAP-2, the importance of platelets in the media, which elaborate the precursor of NAP-2, and suppression of the chemotactic response by serine protease inhibitors, which would block the monocyte-derived serine esterase that creates NAP-2 from its immediate precursor. Consistent with this conclusion is inhibition of the chemotactic response to monocytes by agents that block CXCR2, the receptor that NAP-2 uses. Later, when the monocyte moves from the center of chemoattraction, the activated PMN themselves, whose own chemotactic properties are enhanced in EDTA/plasma, appear to take over generation of the gradient, resulting in a prolonged ingress of PMN from outside the field (“second wave”). Chemoattraction by monocytes seems to be simply one way of stimulating the PMN, which, once activated, fail in EDTA/plasma to efficiently shut off their own chemoattraction for other PMN. We suggest that these exaggerated chemotactic effects are due to the loss of normal modulation by a regulatory factor(s) designed to keep the chemotactic response from getting out of hand—i.e., a tonic inhibitor of chemotaxis in plasma.