bluuebunny/crossref_metadata_2025_split huggingface dataset:
NADPH oxidase is functionally assembled in specific granules during activation of human neutrophils
Authors: Vaissiere Clémence , Le Cabec Véronique , Maridonneau-Parini Isabelle 
Published: January 2018

Abstract
In addition to the extracellular production of O2− by NADPH oxidase in neutrophils stimulated by soluble stimuli, the intracellular formation of oxygen reactive species has been described. Cytochrome b559, the redox component of the NADPH oxidase complex, is mainly associated with specific granule membrane in resting neutrophils. We examined whether these granules could be a site for intracellular production of O2−. Phorbol myristate acetate (PMA)-stimulated neutrophils were fractionated by differential centrifugation, and generation of O2− was detected in both the granule and the plasma membrane-enriched fractions, but more in the granules. Translocation of p47phox and p67phox, two cytosolic components of the NADPH oxidase, was also quantitatively more important in the granules than in the plasma membrane fraction. After separation of the specific from the azurophil granules, p47phox and p67phox were found to be present only in the specific granules of PMA-activated cells. As a control, the production of O2− was studied in retinoic acid-differentiated NB4 cells that lack specific granules. During stimulation of NB4 cells with PMA, only the plasma membrane-enriched fraction was the site of O2− production. Together, these results indicate that NADPH oxidase can be functionally assembled in specific granules. J. Leukoc. Biol. 65: 629–634; 1999.
Cloning of two chemokine receptor homologs (CXC-R4 and CC-R7) in rainbow trout Oncorhynchus mykiss
Authors: Daniels Garry D , Zou Jun , Charlemagne Jacques , Partula S , Cunningham Charles , Secombes Christopher J 
Published: January 2018

Abstract
Two rainbow trout chemokine receptors have been sequenced, with homology to CXC-R4 and CC-R7 molecules. The CXC-R4 sequence consisted of 1681 nucleotides, which translated into a mature protein of 357 amino acids, with 80.7% similarity to human CXC-R4. The CC-R7 sequence consisted of 2287 nucleotides, which translated into a 368-amino acid mature protein with 64.5% similarity to human CC-R7. Both sequences contained seven hydrophobic regions, representing the seven transmembrane domains (TM) typical of G-protein-coupled receptors. Extracellular cysteines, transmembrane prolines, and the DRY motif immediately following TM3 were conserved. Phylogenetic tree analysis revealed a tight clustering of trout CXC-R4 with CXC-R3-5 genes. Trout CC-R7 clustered with CC-R6-7 and CXC-R1-2. Reverse transcriptase-polymerase chain reaction analysis demonstrated a wide tissue distribution of CXC-R4 and CC-R7 message in trout, being present in head-kidney leukocytes, blood, gill, brain, spleen, and liver. J. Leukoc. Biol. 65: 684–690; 1999.
Dysregulation of PMN antigen expression in Type 2 diabetes may reflect a generalized defect of exocytosis: influence of hypertension and microalbuminuria
Authors: Senior Peter A , Marshall Sally M , Thomas Trevor H 
Published: January 2018

Abstract
Defective exocytosis could underlie clinical and metabolic abnormalities in Type 2 diabetes. Because many SNARE proteins appear to be common mediators of exocytosis, we examined phorbol myristate acetate-stimulated expression of CD11b and CD69 on polymorphonuclear leukocytes (PMN) from Type 2 diabetic subjects with hypertension and microalbuminuria (D-htma), hypertension only (D-ht) or uncomplicated (D-uc), and normal controls (NC) by flow cytometry. CD11b expression was rapid (half maximal by 7 min), initially on all PMN. CD69 expression took place subsequently but on PMN that did not express CD11b. The proportion of CD11b-positive PMN at 30 min was higher in all diabetic groups than in NC. Expression of CD11b was higher and CD69 lower in D-uc and D-htma but were similar in NC and D-ht. In Type 2 diabetes the transition from the CD11b-positive to CD69-positive state is impaired. The defect in the process of CD69 expression appeared most marked in diabetic subjects with hypertension and microalbuminuria. J. Leukoc. Biol. 65: 800–807; 1999.
Mycoplasma arginini enhances cytotoxicity of thioglycollate-elicited murine macrophages toward YAC-1 tumor cells through production of NO
Authors: Ribeiro-Dias Fátima , Russo Momtchilo , Marzagão Barbuto José Alexandre , Raquel Flávia , do Nascimento Fernandes , Timenetsky Jorge , Jancar Sonia 
Published: January 2018

Abstract
Bacterial products stimulate macrophage tumoricidal activity through release of tumor necrosis factor (TNF) and nitric oxide (NO). We show here that thioglycollate-elicited macrophages acquire cytotoxic activity when cocultured with Mycoplasma arginini-infected YAC-1 tumor cells and release TNF and NO. Fixed mycoplasma-infected cells, supernatants from infected-cell cultures, or purified heat-killed mycoplasma obtained from cell-free cultures were all able to induce TNF and NO production. Thus, the mycoplasma per se and not a product of infected cells induce the release of these molecules. Addition of prostaglandin E2 (PGE2) to the cocultures, which reduced TNF release, or antibodies to TNF, did not affect macrophage cytotoxicity nor NO release. Inhibition of NO production by L-NAME or aminoguanidine reduced the cytotoxicity, and treatment with a NO donor was toxic to YAC-1 cells. These results indicate that M. arginini activates thioglycollate-elicited murine macrophages for NO and TNF release increasing their cytotoxic activity toward YAC-1 cells and that this activity is dependent on NO but not TNF release. J. Leukoc. Biol. 65: 808–814; 1999.
Identification of the CD85 antigen as ILT2, an inhibitory MHC class I receptor of the immunoglobulin superfamily
Authors: Banham Alison H , Colonna Marco , Cella Marina , Micklem Kingsley J , Pulford Karen , Willis Antony C , Mason David Y 
Published: January 2018

Abstract
The CD85 molecule was originally defined at the Fifth Workshop on Leucocyte Antigens in 1993 by two monoclonal antibodies, VMP55 and GHI/75. This cell-surface glycoprotein is expressed on B cells, monocytes, and subpopulations of T and natural killer (NK) cells, and particularly high levels are expressed by normal and neoplastic plasma cells and by hairy cell leukemia B cells. We affinity purified the CD85 antigen and obtained tryptic peptide sequence which indicated that this molecule might be ILT2, a recently described inhibitory major histocompatibility complex class I receptor of the immunoglobulin superfamily. This was confirmed by showing that both of the original anti-CD85 mAbs stained ILT2 transfectants. The cell signaling role demonstrated for ILT2 is consistent with the previously reported involvement of CD85 in T cell activation. J. Leukoc. Biol. 65: 841–845; 1999.
Protein kinase C and a calcium-independent phospholipase are required for IgG-mediated phagocytosis by Mono-Mac-6 cells
Authors: Karimi Kambiz , Gemmill Trent R , Lennartz Michelle R 
Published: January 2018

Abstract
Mono-Mac-6 (MM6) human monocytes ingest IgG-opsonized particles better than other human cell lines. We compared the phagocytic signaling pathway in MM6 with human monocytes. MM6 expressed FcγRI at levels similar to monocytes, whereas FcRγII expression was approximately double. MM6 ingested IgG-opsonized erythrocytes (EIgG) in a calcium-independent manner. Incubation of MM6 with bromoenol lactone, an inhibitor of the phagocytic phospholipase (pPL), coordinately decreased phagocytosis and pPL activity. This inhibition was overcome by exogenous arachidonic acid, suggesting that phagocytosis requires pPL activation and arachidonic acid release. MM6 phagocytosis was inhibited with staurosporine and activated with diacylglycerol, supporting a role for protein kinase C (PKC) in this process. The pPL activators mastoparan and melittin restored phagocytosis to PKC-inhibited cells, suggesting that pPL lies downstream from PKC. These results suggest that the MM6 signal transduction pathway for IgG-mediated phagocytosis is similar to that of monocytes (PKC→pPL→arachidonic acid→phagocytosis). The results are discussed in the context of the finding that MM6 exhibit low phagocytosis relative to monocytes and thus may represent an attractive cell line for molecular manipulation in “recovery of function” studies. J. Leukoc. Biol. 65: 854–862; 1999.
Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells
Authors: Kirken Robert A , Erwin Rebecca A , Taub Dennis , Murphy William J , Behbod Fariba , Wang Lihua , Pericle Federica , Farrar William L 
Published: January 2018

Abstract
Janus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (γc). Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease (SCID) in humans and mice. These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b (STAT5a/b). Similar inhibitory effects were observed with other cytokines that use γc. AG-490 also inhibited IL-2-mediated proliferative growth in human T cells with an IC50 = 25 μM that was partially recoverable. Moreover, we demonstrate that this inhibitor prevented tetanus toxoid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells. Taken together, these findings suggest that AG-490 inhibits the JAK3-mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell-derived pathologies such as graft-versus-host disease, allergy, and autoimmune disorders. J. Leukoc. Biol. 65: 891–899; 1999.
MHC class II-dependent activation of CD4+ T cell hybridomas by human mast cells through superantigen presentation
Authors: Poncet Pascal , Arock Michel , David Bernard 
Published: January 2018

Abstract
Human mast cells (MC) were examined for expression of MHC class II antigens and for their ability to activate CD4+ T cell hybridomas through presentation of superantigen (SAg). HMC-1, a leukemic immature MC line expressing class II Ags, was shown to efficiently present the staphylococcal enterotoxin B (SEB) SAg to responding T cell hybridoma on treatment with interferon-γ (IFN-γ), which up-regulated class II molecules. The study was then extended to human normal MC. Almost pure (&gt;99%) cord blood-derived MC (CBMC) were shown to express class II Ags (HLA-Dr and HLA-DQ) and CD80, which were up-regulated by IFN-γ treatment and, to a lesser extent, by interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). CBMC directly activated CD4+ T cell hybridomas through presentation of SEB and TSST1 SAgs. The production of IL-2 required a cell-to-cell contact between T cells and CBMC and it was inhibited by anti-class II antibodies. Furthermore, an additional pretreatment of CBMC by IFN-γ or GM-CSF or IL-4 had no effect on their presenting efficiency. This previously unknown function of human MC, i.e., MHC class II-dependent activation of CD4+ T cells, may be critical in subsequent cellular activation events because colocalization of mast and T cells is frequently observed at sites of antigen entry. J. Leukoc. Biol. 66: 105–112; 1999.
Adhesion and homing of blood-borne cells in bone marrow microvessels
Authors: Mazo Irina B , von Andrian Ulrich H 
Published: January 2018

Abstract
After birth, the bone marrow (BM) is the principal site of hematopoiesis in mammals. Thus, a large number of newly formed blood cells must penetrate the wall of BM microvessels to enter the circulation. In addition, the BM appears to function as a lymphoid organ and is also part of the macrophagal system. Subsets of circulating lymphocytes and other cells of the immune system continuously home to the BM. However, neither the mechanisms of blood cell migration to and from the BM nor its precise role in the immune system are well understood. One reason for the relative paucity of data on BM physiology is the fact that normal BM is surrounded by thick cortical bone that impedes direct observation and experimental manipulation. One notable exception is the calvaria of the murine skull where hematopoietically active BM is only covered by a thin lamella of bone that is sufficiently translucent to allow a detailed in situ analysis of the BM microcirculation by epi-fluorescence microscopy. Here, we review our current knowledge of the anatomic, hemodynamic, and endothelial properties of the specialized microvascular bed within murine skull BM. In addition, we summarize recent studies on the molecular mechanisms that mediate the homing of circulating hematopoietic progenitor cells to the BM, an event that is critical for the success of BM transplantations. J. Leukoc. Biol. 66: 25–32; 1999.
Involvement of caveolae in the uptake of respiratory syncytial virus antigen by dendritic cells
Authors: Werling Dirk , Hope Jayne C , Chaplin Paul , Collins Robert A , Taylor Geraldine , Howard Chris J 
Published: January 2018

Abstract
The uptake of respiratory syncytial virus (RSV) antigen by cattle dendritic cells was investigated. Pathways of antigen uptake were monitored by flow cytometry using specific tracers and by proliferation assays, which were used to measure the presentation of RSV antigen and ovalbumin. Inhibitors that differentially affected pathways were used to distinguish them. Presentation of RSV antigen, but not ovalbumin, was inhibited by phorbol myristate acetate and filipin, which have been reported to inhibit caveolae, but not by cytochalasin D, amiloride, or mannose. These inhibitors have been reported to block macropinocytosis and other actin-dependent uptake mechanisms, endocytic pathways involving clathrin-coated pits, and the mannose receptor. Furthermore, co-localization of RSV antigen and caveolae was observed by confocal microscopy. Thus, the major route for uptake of RSV antigen by cattle dendritic cells is one mediated by caveolae, adding a pathway of antigen uptake by dendritic cells to those established. J. Leukoc. Biol. 66: 50–58; 1999.
Respiratory syncytial virus infection of human respiratory epithelial cells enhances inducible nitric oxide synthase gene expression
Authors: Tsutsumi Hiroyuki , Takeuchi Ryoh , Ohsaki Masaya , Seki Kimihira , Chiba Shunzo 
Published: January 2018

Abstract
The induction kinetics of the mRNA of interferon regulatory factor 1 (IRF-1), inducible nitric oxide synthase (iNOS), and proinflammatory cytokines in respiratory syncytial virus (RSV)-infected human type 2 alveolar epithelial cells (A549 cells) were analyzed semiquantitatively by RT-PCR. RSV enhanced IRF-1 and iNOS mRNA expression as early as 4 h after RSV infection and this enhancement lasted several hours. No IFN-γ gene expression was observed during the whole course of the infection. Expression of IFN-β, IL-1β, and TNF-α genes was observed slightly at 4 h and became marked 7 h after infection. Addition of neutralizing antibodies to these cytokines to the culture had no effect on the induction of iNOS mRNA. The iNOS transcriptional activity in RSV-infected cells was significantly enhanced by an exogenous cytokine mixture (IL-1β, TNF-α, and IFN-γ). An apparent nitric oxide (NO) production was identified only when cytokines were added together with RSV infection. A significant increase of iNOS gene expression was observed in nasopharyngeal exudate cells obtained from infants during the acute phase of RSV bronchiolitis. These observations suggest that RSV infection of human respiratory epithelial cells induces the iNOS gene both in vitro and in vivo; this induction may occur rather promptly and involves transcriptional activator IRF-1 induced by the RSV infection itself. The iNOS gene, which is initially induced by RSV infection, may be further enhanced in a paracrine fashion by proinflammatory cytokines released by infection-activated inflammatory cells. J. Leukoc. Biol. 66: 99–104; 1999.
Positive and negative regulation of the myeloid dendritic cell lineage
Authors: Santiago-Schwarz Frances 
Published: January 2018

Abstract
Recent advances have revealed that dendritic cells (DCs) are not a single cell type, but a system of cells that are phenotypically and functionally diverse. DC subtypes stemming from the myeloid and lymphoid lineages promote a diversity of immune responses ranging from the stimulation of naive T and B cell responses to the down-regulation of T cell responses. Although differences in antigen handling are linked to DC developmental stages in the myeloid DC lineage, the particular type of immune response elicited may be determined by a specific DC subtype. This review summarizes key regulatory mechanisms controlling the development of myeloid lineage DCs from multipotent progenitors. Emphasis is placed on describing a highly orchestrated series of proliferative, apoptotic, and developmental events involving granulocyte-macrophage colony-stimulating factor, transforming growth factor β, and the tumor necrosis factor α, CD95, and bcl-2 protein families. J. Leukoc. Biol. 66: 209–216; 1999.
Myb-transformed hematopoietic cells as a model for monocyte differentiation into dendritic cells and macrophages
Authors: Banyer Joanne L , Hapel Andrew J 
Published: January 2018

Abstract
Immune induction is effected through the interaction of antigen-presenting cells with specific receptors on the surface of thymus-derived lymphocytes. Cells most able to ingest, process, and present antigen appear to be related to the mononuclear phagocyte/neutrophil series. For example dendritic cells (DC) can be found in colonies of GM-CSF-responsive bone marrow cells, and under experimental conditions are routinely expanded as a population in vitro from GM-CSF-responsive progenitor cells. To address the question of DC lineage and to determine what genes are involved in lineage commitment, we have generated a series of GM-CSF-responsive cell lines that can be induced to differentiate in a homogeneous manner in vitro. The cloned cell lines are derived from 12-day fetal liver and are transformed with a truncated form of c-myb, which lacks the normal autoregulatory sequences. As far as we know, these myb-transformed hemopoietic cells (MTHC) differ from normal only in the unregulated expression of myb, a gene whose expression is obligatory for proliferation of hemopoietic cells. MTHC in the presence of TNF-α and IL-4 will differentiate into cells that have many of the properties of macrophages. When the same MTHC lines are exposed to TNF-α in combination with IFN-γ, the cells instead become DC. The differentiated DC are potent presenters of antigen in mixed lymphocyte reactions and of soluble antigen to specific T cell lines. Thus, cells with the properties of both macrophages and DC can be derived from a single type of GM-CSF-responsive progenitor cell. We have used this MTHC system to analyze differences in gene expression as the cells mature along the DC and macrophage pathways. A distinctive pattern of differentially expressed cDNAs is evident where macrophage-specific cDNAs are homologous to genes encoding cytoskeletal and cell-surface proteins, whereas the DC-specific cDNAs are homologous to signaling, chemokine, and IFN-γ-inducible genes. We discuss the utility of MTHC in analyzing the relationships between DC and macrophages, and suggest that DC and macrophages represent extreme phenotypes in a spectrum of antigen handling cells that are somewhat interchangeable, depending on their immediate environment. J. Leukoc. Biol. 66: 217–223; 1999.
Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines
Authors: Dieu-Nosjean Marie-Caroline , Vicari Alain , Lebecque Serge , Caux Christophe 
Published: January 2018

Abstract
DC function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led to the investigation of the chemokine responsiveness of DC during their development and maturation. These studies have shown that immature and mature DC are not recruited by the same chemokines. Immature DC respond to many CC- and CXC-chemokines (MIP-1α, MIP-1β, MIP-5, MCP-3, MCP-4, RANTES, TECK, and SDF-1) and in particular to MIP-3α/LARC, which acts through CCR6, a receptor mainly expressed in DC and lymphocytes. Like most other chemokines acting on immature DC, MIP-3α is inducible on inflammatory stimuli. In contrast, mature DC have lost their responsiveness to most of these chemokines through receptor down-regulation or desensitization, but acquired responsiveness to MIP-3β/ELC and 6Ckine/SLC as a consequence of CCR7 up-regulation. MIP-3α mRNA is only detected within inflamed epithelial crypts of tonsils, the site of antigen entry known to be infiltrated by immature DC, whereas MIP-3β and 6Ckine are specifically expressed in the T cell-rich areas where mature IDC home. These observations suggest a role for chemokines induced on inflammation such as MIP-3α in recruitment of immature DC at the site of injury and a role for MIP-3β/6Ckine in accumulation of antigen-loaded mature DC in T cell-rich areas of the draining lymph node. A better understanding of the regulation of DC trafficking might offer new opportunities of therapeutic interventions to suppress or stimulate the immune response. J. Leukoc. Biol. 66: 252–262; 1999.
Retroviral gene transfer, rapid selection, and maintenance of the immature phenotype in mouse dendritic cells
Authors: Gasperi C , Rescigno M , Granucci F , Citterio S , Matyszak M K , Sciurpi M T , Lanfrancone L , Ricciardi-Castagnoli P 
Published: January 2018

Abstract
We used the retroviral vector PINCO [which expresses the green fluorescent protein (GFP) as a selectable marker], to infect growth factor-dependent immature D1 dendritic cells (DC). The efficiency of infection in different experiments was between 5 and 30%, but subsequent cell sorting led to a virtually homogeneous population of GFP-positive cells. Retroviral infection did not modify the immature DC phenotype, as shown by the low expression of major histocompatibility complex and co-stimulatory molecules. Furthermore, the GFP-positive D1 cells underwent full maturation after lipopolysaccharide treatment, as indicated by a high expression of cell-surface MHC and co-stimulatory molecules, and also by strong stimulatory activity in allogeneic mixed lymphocyte reaction. The high efficiency of this retroviral system, the rapidity of the technique, and the possibility to overcome in vitro selection make this method very attractive for the stable introduction of heterologous genes into proliferating immature mouse D1 cells. Furthermore, this approach is suitable for functional studies of new DC-specific genes involved in DC maturation and survival. J. Leukoc. Biol. 66: 263–267; 1999.