bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon-γ inhibits HIV-induced invasiveness of monocytes
Authors: Dhawan Subhash , Wahl Larry M , Heredia Alonso , Zhang Yahong , Epstein Jay S , Meltzer Monte S , Hewlett Indira K 
Published: January 2018

Abstract
HIV-infected monocytes form highly invasive network on basement membrane matrix and secrete high levels of 92-kd metalloproteinase (MMP-9), an enzyme that degrades basement membrane proteins. In the present study, using matrigel as a model basement membrane system, we demonstrate that treatment of human immunodeficiency virus (HIV)-infected monocytes with interferon-γ at 50 U/ml inhibited the ability of infected monocytes to form an invasive network on matrigel and their invasion through the matrigel matrix. These effects were associated with a significant reduction in the levels of MMP-9 produced by HIV-infected monocytes treated with interferon-γ 1 day prior to infection with HIV as compared with that of untreated HIV-infected monocytes. Monocytes treated with interferon-γ 1 day after HIV infection showed the presence of integrated HIV sequences; however, the levels of MMP-9 were substantially lower than those produced by monocytes inoculated with live HIV, heat-inactivated HIV, or even the control uninfected monocytes. Exposure of monocytes to heat-inactivated HIV did not result in increased invasiveness or high MMP-9 production, suggesting that regulation of metalloproteinase by monocytes was independent of CD4-gp120 interactions and required active virus infection. Furthermore, addition of interferon-γ to monocytes on day 10 after infection inhibited MMP-9 production by more than threefold with no significant reduction of virus replication. These results indicate that the mechanism of interferon-γ–induced down-regulation of MMP-9 levels and reduced monocyte invasiveness may be mediated by a mechanism independent of antiviral activity of IFN-γ in monocytes. Down-regulation of MMP-9 in HIV-infected monocytes by interferon-γ may play an important role in the control of HIV pathogenesis.
New members of the chemokine receptor gene family
Authors: Raport Carol J , Schweickart Vicki L , Chantry David , Eddy Roger L , Shows Thomas B , Godiska Ronald , Gray Patrick W 
Published: January 2018

Abstract
Chemokines are relatively small peptides with potent chemoattractant and activation activities for leukocytes. Several chemokine receptors have been cloned and characterized and all are members of the G protein-coupled receptor superfamily. Using degenerate oligonucleotides and polymerase chain reaction, we have identified seven novel receptors with significant homology to chemokine receptors. Two of these sequences are presented here for the first time. We have shown, with gene mapping studies, that receptors with the highest sequence similarity are closely linked on human chromosomes. This close genetic association suggests a functional relationship as well.
The role of MIP-1α in Inflammation and hematopoiesis
Authors: Cook Donald N 
Published: January 2018

Abstract
Macrophage inflammatory protein 1α (MIP-1α) is a member of the C-C subfamily of chemokines, a large superfamily of low-molecular-weight, inducible proteins that exhibit a variety of proinflammatory activities in vitro including leukocyte Chemotaxis. MIP-1α is a particularly interesting chemokine, because in addition to its proinflammatory activities, it inhibits the proliferation of hematopoietic stem cells in vitro and in vivo. Here, the biologic properties of MIP-1α are reviewed in light of recent data on mice homozygous for a disruption of the MIP-1α gene. The MIP-1α null mice have no overt abnormalities of peripheral blood or bone marrow cells, indicating that MIP-1α is not necessary for normal hematopoiesis. However, the MIP-1α null mice have a reduced inflammatory response to influenza virus and are resistant to coxsackievirus-induced myocarditis. These data demonstrate that MIP-1α is required for a normal inflammatory response to these viruses. Agents that inhibit the action of MIP-1α may therefore prove useful for controlling inflammation in these and other settings.
β Chemokines costimulate lymphocyte cytolysis, proliferation, and lymphokine production
Authors: Taub Dennis D , Ortaldo John R , Turcovski-Corrales Susan M , Key Michael L , Longo Dan L , Murphy William J 
Published: January 2018

Abstract
We report here the ability of the β chemokines MIP-1α, MP-1β, RANTES, and MCP-1 to enhance some lymphocyte effector functions. Initial studies focused on the effects of chemokines on human and mouse cytotoxic T lymphocyte (CTL)–and natural killer (NK) cell–specific cytolytic responses. The results demonstrate that β chemokines are capable of augmenting mouse and human CTL and human NK–but not lymphokine-activated killer cell– or antibody-dependent cell cytotoxicity–specific cytolytic responses. Neutralisation analysis utilizing integrin-specific antibodies revealed that CTL/NK–tumor cell conjugate formation is required for chemokine-induced killing. In addition, both CTLs and NK cells incubated with various β chemokines were induced to degranulate and release granule-derived serine esterases, suggesting that chemokines may be important costimulators of CTL and NK cell degranulation and may thus augment local target cell destruction. Chemokines also modulate antigen-driven T cell proliferative responses as well as effects on lymphokine production. Many of the β chemokines were found to potentiate human and mouse antigen-specific Th1 and Th2 clone activation promoting cellular proliferation and the release of various lymphokines. This chemokine-mediated T cell proliferation was chemokine and antigen dose dependent as well as clone dependent. Chemokine pretreatment analyses with T cells and antigen-presenting cells (APCs) revealed that chemokines up-regulate both T cell and APC functions. Costimulation assays using immobilized anti-CD3 monoclonal antibody–coated plates and purified human and mouse T cells and T cell clones in the presence of various chemokines also exhibited enhanced proliferation and lymphokine secretion. This costimulation was interleukin-2 dependent and required the presence of free extracellular calcium. Examination of chemokine-treated APCs revealed that the T cell costimulatory molecule B7-1 was induced by various β chemokines. Neutralization of endogenously produced chemokines with specific antibodies during an antigen-specific T cell response blocked cellular proliferation, suggesting that the chemokines have an autocrine and/or paracrine role in antigen-induced T cell proliferative responses. Together, these results suggest that chemokines play a significant role in the activation of polyclonal as well as antigen-specific helper and cytotoxic T cells during the genesis of an immune response.
Role of yolk sac endodermal cells with special reference to the fetal macrophage differentiation
Authors: Yamashita Akira 
Published: January 2018

Abstract
The morphological and functional characteristics of rat yolk sac endodermal cells, with particular reference to fetal macrophage (Mφ differentiation, were studied in vivo and in vitro using DA rat embryos from 8 to 16 days of gestation. At a very early stage (day 5–6) of gestation, endodermal cells are derived from proximal endoderm as an essential and multipotent organ with various primitive functions. Based on toluidine blue staining properties and ultrastructures, we demonstrated that the endodermal cell layer of 8–16-day yolk sacs consists of two cell types, “clear” cells with clear cytoplasm (10%) and “dark” cells with dark cytoplasm (90%), and hypothesized that the endodermal cell layer is heterogeneous at both the morphological and functional levels. We produced three different monoclonal antibodies (mAbs), designated Mar 1, Mar 2, and Mar 3, that recognize rat Mφ populations. Mar 1 binds specifically to the cells constituting the mononuclear phagocyte system (MPS). Mφ Mar 3 antigen is a phagocytosis-associated molecule, and Mar 2 antigen is a differentiation antigen of the Mφ subset. Application of these mAbs in both in vivo and in vitro studies allowed the functional capability and differentiation of fetal Mφs to be assessed. The Mar 3 antigen was expressed first on proximal endodermal cells on day 6 yolk sac and continued to be presented afterward. In vitro culture study demonstrated that the adhesive, phagocytic Mar 3+ · Mar 1+ Mφs differentiate from Mφ precursors in the endodermal cell layer after the first 13 days of gestation. Based on these findings, we proposed that clear cells in the endodermal cell layer are derived from precursor dark cells, detach from the layer, move to the mesenchymal stromas, and subsequently migrate to the fetal liver, loose connective tissue, and other intraembryonic tissues, and consequently they differentiate free Mar 1+ Mφs during gestation (day 13–15). Thus, the Mφ differentiation and the peripherization of the Mφs could be almost fully developed during the prenatal period.
Alkyl-PAF and acyl-PAF human neutrophil priming for enhanced fMLP- and rC5a-induced superoxide anion production
Authors: Pinckard R Neal , Prihoda Thomas J 
Published: January 2018

Abstract
Alkyl-PAF induced two components of polymorphonuclear leukocyte (PMN) pruning for enhanced fMLP- and rC5a-induced superoxide anion (O2−) production. Component A priming had a shallow, linear alkyl-PAF concentration-response slope (10 pM–1 nM), and component B priming had a significantly steeper concentration-response slope (1–100 nM alkyl-PAF). Whereas the extent of component B priming decayed significantly within 5–10 min after pretreatment of PMNs with alkyl-PAF, component A priming was completely stable. WEB 2086, a specific and potent PAF receptor antagonist, abolished component A pruning when PMNs were simultaneously stimulated with alkyl-PAF and either fMLP or rC5a but only partially reduced component B priming. However, whereas WEB 2086 also obliterated component A priming when PMNs were pre-treated with alkyl-PAF for 2.5, 5, or 10 min prior to fMLP stimulation, WEB 2086 had little or no inhibitory effect on component B priming. Paradoxically, WEB 2086 significantly augmented alkyl-PAF–induced component B priming for enhanced rC5a-induced PMN O2− production yet concomitantly obliterated component A printing. PMN pruning by acyl-PAF (1 nM–1 μM) had characteristics identical to those of alkyi-PAF–induced component A priming. These studies suggest that there are at least two effector pathways modulating alkyl-PAF–induced PMN respiratory burst priming. They are also consistent with the notion that component A priming is initiated via high-affinity PAF receptors and component B priming is mediated through low-affinity PAF receptors; and whereas alkyl-PAF interacts with both high- and low-affinity PAF receptors, both acyl-PAF and WEB 2086 preferentially bind to the high-affinity PAF receptors.
Soluble CD14 and lipopolysaccharide-binding protein from bovine serum enable bacterial lipopolysaccharide-mediated cytotoxicity and activation of bovine vascular endothelial cells in vitro
Authors: Yang Zhengang , Breider Michael A , Carroll Roger C , Miller Mark S , Bochsler Philip N 
Published: January 2018

Abstract
Bacterial endotoxin (lipopolysaccharide, LPS) has potent proinflammatory properties toward many cell types, including vascular endothelial cells. Bovine endothelial cells are often used for investigations involving the vascular endothelium in vitro, and other bovine products such as fetal bovine serum are also widely utilized in research laboratories. Evidence is presented that soluble CD14 (sCD14) is present in bovine serum and that LPS-mediated activation and cytotoxicity to bovine endothelial cells in vitro are dependent on sCD14. LPS-mediated activation of endothelial cells was quantitated by measuring tissue factor expression using an activated factor X–related chromogenic assay. Concentrations of 0.1–5.0% fetal bovine serum in the culture medium promoted LPS-induced tissue factor expression on bovine endothelial cells, and anti-CD14 monoclonal antibody (mAb) (20 μg/ml) inhibited tissue factor expression, whereas control antibodies did not. LPS-mediated damage to endothelial cells was assayed using the MTT tetrazolium assay. We found that either serum or recombinant human soluble CD14 (rsCD14, 20–2000 ng/ml) was required for LPS-related endothelial cell damage and that anti-CD14 mAb inhibited cytotoxicity. In addition, bovine LPS-binding protein (LBP, 20 ng/ml) purified from bovine serum had no effect on LPS-mediated cytotoxicity, but bovine LBP greatly enhanced the cytotoxic effect of LPS plus rsCD14. Western blot analysis performed on fractionated bovine serum samples with anti-CD14 mAb revealed immunoreactivity with a 50–55-kd protein, a size consistent with sCD14. Evidence of endothelial cell-associated CD14 was not detected using an immunofluorescence technique on cell preparations, nor by Northern blot analysis. These results indicate the existence of sCD14 in bovine serum and that soluble bovine serum factors including sCD14 and LBP facilitate presentation of LPS to receptive cells.
Phorbol myristate acetate-induced NADPH oxidase activity in human neutrophils: only half the story has been told
Authors: Lundqvist Helen , Foilin Per , Khalfan Laila , Dahlgren Claes 
Published: January 2018

Abstract
The paradigm for activation of the neutrophil NADPH oxidase with the protein kinase C activator phorbol myristate acetate (PMA) states that the oxidase assembles in the plasma membrane and that the metabolites generated are released extracellularly. This paradigm is challenged by the results presented. Most of the PMA-induced oxidase activity measured as chemiluminescence and dichlorofluorescein fluorescence was insensitive to scavengers of superoxide anion and hydrogen peroxide. This indicates that oxidase activity also takes place in a cellular compartment that the scavengers cannot reach. From the results obtained with granule-deficient HL-60 cells and cord blood neutrophils, we suggest that the scavenger-insensitive part of the NADPH oxidase activity in normal neutrophils re-sides in an intracellular compartment identical to or originating from granules. Our results also indicate that specific and azurophil granules have to be in very close contact to allow the generated oxygen metabolites to reach and react with myeloperoxidase.
Computerized assessment of production of multiple human cytokines at the single-cell level using image analysis
Authors: Björk Lars , Fehniger Thomas E , Andersson Ulf , Andersson Jan 
Published: January 2018

Abstract
A technique using a computerized image analysis system was developed for evaluating and quantifying human cytokine production. This system registered single cells as positive or negative cytokine producers based on a specific juxtanuclear staining pattern generated by accumulation of the proteins in the Golgi-endoplasmatic reticulum compartment. The characteristic morphology of the immunocytochemical staining offered the opportunity to register individual producer cells within multicomponent cell populations. A color camera was then adapted to transfer on-line images directly into the computer-controlled operating system. In this study cultured human peripheral blood mononuclear cells were polyclonally stimulated and then analyzed for interleukin-1α (IL-1α), IL-1β, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), TNF-β, interferon-γ, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor production. The image-analyzing system detected cytokine-producing cells in a sensitive and reproducible manner, which was in total congruence with enumeration by conventional microscopy. Furthermore, accurate assessments of cell distributions by signal intensity and cell area were applied at the single-cell level. The image-analyzing system allowed the detection of at least 1 in 1,000 events by using unique cytokine-associated morphometric criteria. The results of kinetic studies measuring cytokine production following activation and cell transformation provided data supporting increases in intensity of intracellular localized specific immunostaining and in cell size within the cytokine-producing cells.
Rapid secretion of intracellularly pre-stored interleukin-8 from rabbit platelets upon activation
Authors: Su Shao-Bo , Mukaida Naofumi , Matsushima Kouji 
Published: January 2018

Abstract
Freshly isolated rabbit platelets contained a substantial amount of intracellular interleukin-8 (IL-8) as revealed by immunohistochemistry and Western blotting analysis. Thrombin stimulation at room temperature induced platelets to secrete IL-8 rapidly, and the maximal secretion was observed within 10 min after the activation. Secreted IL-8 possessed neutrophil chemotactic activity that was neutralised by a specific neutralizing monoclonal antibody to rabbit IL-8 but not a control one. These results suggest that rabbit platelets store biologically active IL-8 intracellularly and secrete it rapidly upon activation. This study implies that platelets may be a pivotal participant in inflammatory reactions in rabbits through producing cytokines and chemokines, including IL-8.
The inflammatory response in interleukin-1β-deficient mice: comparison with other cytokine-related knock-out mice
Authors: Fantuzzi Giamila , Dinarello Charles A 
Published: January 2018

Abstract
Interleukin-1 (IL-1) plays a crucial role in the development of the pathophysiological responses to infection and inflammation. However, the relative contributions of IL-1α and IL-1β remain to be clarified. IL-1β-deficient mice are a powerful tool to investigate the specific role of IL-1β in various experimental conditions. In this report, we summarize the response of IL-1β-deficient mice to two different inflammatory stimuli, turpentine and endotoxin. Although IL-1β-deficient mice respond normally to the systemic administration of lipopolysaccharide (LPS), they do not develop an acute-phase response in the localized tissue damage model of turpentine injection. The results obtained using the IL-1β-deficient mice are compared here with those observed in the IL-1β-converting enzyme-deficient, IL-6-deficient, tumor necrosis factor-receptor p55-deficient, and interferon-γ-receptor-deficient mice.
The lectin jacalin triggers CD4-mediated lymphocyte signaling by binding CD4 through a protein-protein interaction
Authors: Lafont Virginie , Domand Jacques , Covassin Laurence , Liautard Jean Pierre , Favero Jean 
Published: January 2018

Abstract
The lectin jacalin specifically stimulates lymphocytes expressing the CD4 antigen. Recent studies have also demonstrated that this lectin interacts with CD4, inhibits in vitro HIV infection, and triggers cell signaling directly via CD4. Jacalin as a lectin was suggested to trigger CD4-mediated cell signaling by interacting with the oligosaccharide side chains of CD4 located on Asn271 and Asn300. Such a hypothesis was of importance because it implied that the glycosylated chains could represent a functional domain directly involved in CD4-related cell activation. We analyzed this possibility by studying the effect of hapten sugars on jacalin-induced CD4 cell signaling and jacalin/CD4 interaction, and by studying the binding capacities of the lectin toward glycosylated, deglycosylated, and unglycosylated CD4. The results presented in this study provide evidence that jacalin does not recognize the CD4 oligosaccharide chains and actually binds CD4 through a specific protein-protein interaction; as a consequence these results rule out the involvement of the CD4 saccharide moieties in CD4-mediated cell signaling triggered by the lectin.
The role of calcium in the regulation of apoptosis
Authors: McConkey David J , Orrenius Sten 
Published: January 2018

Abstract
The recognition that apoptosis is regulated by an evolutionarily conserved set of polypeptides from the nematode Caenorhabditis elegant to humans suggests that a conserved set of biochemical mechanism(s) may also be involved in the response. Work from a number of independent laboratories suggests that alterations in cytosolic Ca2+ homeostasis represent one such candidate mechanism, and molecular targets for Ca2+ are now being identified. This review will summarize what is known about the role of Ca2+ in the regulation of apoptosis and discuss how Ca2+ might interact with some of the other biochemical signals implicated in cell death.
Killing of phagocytosed Staphylococcus aureus by human neutrophils requires intracellular free calcium
Authors: Wilsson åsa , Lundqvist Helen , Gustafsson Mikael , Stendahl Olle 
Published: January 2018

Abstract
The mobilization of intracellular calcium plays an important role in regulating neutrophil activation. With this in mind we investigated the effect of intra- and extracellular calcium on the ability of human neutrophils to kill complement-opsonized Staphylococcus aureus. We found that a rise in intracellular calcium is necessary for efficient killing of phagocytosed S. aureus. In the presence of extracellular calcium, killing of ingested bacteria in calcium-buffered neutrophils compared with normal cells was slightly reduced. Calcium buffering had no effect on phagocytic uptake by the neutrophils, but did decrease the generation of toxic oxygen metabolites, measured as chemiluminescence (CL). In non-depleted and calcium-depleted cells, removal of extracellular calcium did not affect ingestion but did cause a marked decrease in the ability to kill the bacteria. In parallel, the CL response was substantially reduced or completely blocked. These data show that calcium is not a prerequisite for phagocytosis of S. aureus by human neutrophils, but does play a vital role in the post-ingestion killing of the bacteria by regulating the generation of toxic oxygen metabolites.
Focal effects of mononuclear leukocyte transendothelial migration: TNF-α production by migrating monocytes promotes subsequent migration of lymphocytes
Authors: de Jong Andrew L , Green David M , Trial JoAnn , Birdsall Holly H 
Published: January 2018

Abstract
In many inflammatory diseases, mononuclear leukocytes (MNLs) accumulate as focal infiltrates in perivascular spaces. We postulated that MNLs migrating through endothelium modify the microenvironment to promote the subsequent migration of additional MNLs into the same area. We found that as monocytes adhere to and migrate spontaneously through an endothelial monolayer, they secrete tumor necrosis fector-α (TNF-α) and interleukin-1. These cytokines stimulate endothelial cell expression of CD54 (intercellular adhesion molecule-1) and CD106 (vascular cell adhesion molecule-1). Consequently, when freshly isolated MNLs are added to that endothelial monolayer four or more hours later, significantly greater numbers of lymphocytes bind to and migrate through these endothelial monolayers. In addition to its ability to activate endothelial cell adhesion molecules, TNF-α induced directed migration of lymphocytes through collagen pads. These results illustrate a potential amplification mechanism by which MNLs moving through a vessel wall may secrete TNF-α, leading to the recruitment of additional leukocytes into the same perivascular locus.