bluuebunny/crossref_metadata_2025_split huggingface dataset:
GM-CSF-transduced B16 melanoma cells are highly susceptible to lysis by normal murine macrophages and poorly tumorigenic in immune-compromised mice
Authors: Kumar Rakesh , Yoneda Junya , Fidler Isaiah J , Dong Zhongyun 
Published: January 2018

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced B16-F10 murine melanoma cells had lower tumorigenicity in both syngeneic and nude mice than parental or LacZ-transduced (control) cells. The subcutaneous (s.c.) tumors producing GM-CSF were densely infiltrated with macrophages, whereas the control tumors were not. In vitro studies showed that GM-CSF-transduced B16 cells were susceptible to lysis mediated by nonactivated murine macrophages, whereas control B16 cells were not. Macrophage-mediated cytotoxicity against GM-CSF-transduced B16 cells was independent of the presence of NO, H2O2, O2-, tumor necrosis factor α, and matrix metalloproteinase. Coculture experiments using GM-CSF-producing and -nonproducing B16 cells demonstrated that GM-CSF produced by the transduced B16 cells activated macrophages to kill the bystander non-GM-CSF-producing tumor cells. The results suggest that GM-CSF released by tumor cells can induce macrophage-mediated cytotoxicity, which in turn can inhibit the in vivo growth of GM-CSF-transduced tumor cells. J. Leukoc. Biol. 65: 102–108; 1999.
Significant expression of G-CSF-induced gene-1 (GIG-1) protein in myeloid cells and NK cells
Authors: Shimane M , Tani K , Hibino H , Setoyama M , Takahashi S , Tojo A , Yodoi J , Asano S 
Published: January 2018

Abstract
The granulocyte colony-stimulating factor (G-CSF)-induced gene, GIG-1, was originally cloned from G-CSF-stimulated bone marrow mononuclear cells obtained from a patient with chronic myelogenous leukemia (CML). We have characterized the GIG-1 gene and its protein product. Expression of GIG-1 mRNA was elevated by treatment with G-CSF in normal bone marrow mononuclear cells, as well as in some cases of blast cells obtained from patients with acute myelogenous leukemia (AML) and CML. Western blot analysis with antiGIG-1 peptide antiserum showed the molecular massofGIG-1 product was about 17 kDa. Immuno-staining of the hematopoietic cells demonstrated that GIG-1 product was mainly localized to the cytoplasm of both myeloid and natural killer (NK) cells. These results suggested that GIG-1 protein is an integral component that is accumulated during the differentiation of myeloid cells toward the stage of mature neutrophils. Expression of GIG-1 gene in mature neutrophils was tightly regulated and reactivation of GIG-1 gene by G-CSF in mature neutrophils may represent a compensation process for the protein lost through the activation of these cells, thus implying an important role for this protein in host defense mechanisms. J. Leukoc. Biol. 65: 109–116; 1999.
Expression of the inducible NO synthase in human monocytic U937 cells allows high output nitric oxide production
Authors: Bertholet S , Tzeng E , Felley-Bosco E , Mauël J 
Published: January 2018

Abstract
Nitric oxide (NO) produced by inducible NO synthase (iNOS, NOS-2) is an important component of the macrophage-mediated immune defense toward numerous pathogens. Murine macrophages produce NO after cytokine activation, whereas, under similar conditions, human macrophages produce low levels or no NO at all. Although human macrophages can express iNOS mRNA and protein on activation, whether they possess the complete machinery necessary for NO synthesis remains controversial. To define the conditions necessary for human monocytes/macrophages to synthesize NO when expressing a functional iNOS, the human monocytic U937 cell line was engineered to synthesize this enzyme, following infection with a retroviral expression vector containing human hepatic iNOS (DFGiNOS). Northern blot and Western blot analysis confirmed the expression of iNOS in transfected U937 cells both at the RNA and protein levels. NOS enzymatic activity was demonstrated in cell lysates by the conversion of L-[3H]arginine into L-[3H]citrulline and the production of NO by intact cells was measured by nitrite and nitrate accumulation in culture supernatants. When expressing functional iNOS, U937 cells were capable of releasing high levels of NO. NO production was strictly dependent on supplementation of the culture medium with tetrahydrobiopterin (BH4) and was not modified by stimulation of the cells with different cytokines. These observations suggest that (1) human monocytic U937 cells contain all the cofactors necessary for NO synthesis, except BH4 and (2) the failure to detect NO in cytokine- stimulated untransfected U937 cells is not due to the presence of a NO-scavenging molecule within these cells nor to the destabilization of iNOS protein. DFGiNOS U937 cells represent a valuable human model to study the role of NO in immunity toward tumors and pathogens. J. Leukoc. Biol. 65: 50–58; 1999.
Priming of human neutrophils by peroxynitrite: potential role in enhancement of the local inflammatory response
Authors: Rohn Troy T , Nelson Laura K , Sipes Karen M , Swain Steve D , Jutila Kathryn L , Quinn Mark T 
Published: January 2018

Abstract
Peroxynitrite is a potent oxidant generated from the reaction of nitric oxide (NO) and superoxide anion (O2−), both of which can be produced in inflammatory tissues. In these studies, we analyzed what direct effect peroxynitrite had on neutrophil (PMN) function. We found that peroxynitrite was an effective priming agent for PMNs, as demonstrated by enhanced O2− production on subsequent activation with low doses of PMA or N-formyl-methionine-leucine-phenylalanine (fMLF), changes in the expression of PMN surface markers (L-selectin, Mac-1, flavocytochrome b, and fMLF receptor), and increased intracellular calcium levels. Analysis of the mechanism of PMN priming by peroxynitrite demonstrated that peroxynitrite resulted in minimal oxidation of protein sulfhydryl groups and subsequent protein cross-linking. In contrast, treatment of PMNs with peroxynitrite resulted in significant nitration of tyrosine residues on neutrophil proteins. In addition, inhibition of tyrosine nitration with a pyrrolopyrimidine antioxidant blocked the majority of peroxynitrite-induced priming effects, further suggesting that PMN priming was mediated primarily by nitration of tyrosine residues on PMN proteins. The ability of peroxynitrite to serve as an effective priming agent for PMNs at sites of inflammation may play a key role in modulating the host-defense process. J. Leukoc. Biol. 65: 59–70; 1999.
Identification of a chicken “C” chemokine related to lymphotactin
Authors: Rossi D , Sanchez-García J , McCormack W T , Bazan J F , Zlotnik A 
Published: January 2018

Abstract
In this study we describe the isolation and characterization of a new chicken (Gallus gallus) chemokine. This molecule belongs to the C or γ-chemokine family and is related to the mouse and human lymphotactin (Lptn). Mouse and human Lptn are distinguished from α and β chemokines by the absence of two cysteines (Cys 1 and 3) that form a disulfide bridge; the novel chicken chemokine shows the same cysteine pattern, but replaces a long carboxy-terminal tail found in the other Lptn proteins with a short extension rich in Arg residues. The 1-kb mRNA is mainly expressed in spleen, although weaker signals have been detected in liver and colon. It is interesting to note that the chicken chemokine seems to preferentially induce the migration of spleen B cells over T cells or B cells from the bursa of Fabricius. J. Leukoc. Biol. 64: 87–93; 1999.
Soluble complement receptor 1 is increased in patients with leukemia and after administration of granulocyte colony-stimulating factor
Authors: Sadallah Salima , Lach Estelle , Schwarz Sybille , Gratwohl Alois , Spertini Olivier , Schifferli Jürg-Alfred 
Published: January 2018

Abstract
Complement receptor type 1 is expressed by erythrocytes and most leukocytes. A soluble form is shed from the leukocytes and found in plasma (sCR1). sCR1 is a powerful inhibitor of complement. We report an increased sCR1 in the plasma of leukemia patients, up to levels producing measurable complement inhibition. Half of the 180 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) had sCR1 levels above the normal range. The highest levels were observed in T-ALL (17 patients). The complement function of a T-ALL serum was improved by blocking sCR1 with a specific mAb (3D9). Measurements in 16 peripheral stem cell donors before and after granulocyte colony-stimulating factor (G-CSF) administration showed an increase in sCR1 (before, 43.8 ± 15.4; at day 5, 118.3 ± 44.7 ng/mL; P &lt; 0.0001). This increase paralleled the increase in total leukocyte counts and was concomitant with de novo leukocyte mRNA CR1 expression in all three individuals tested. Whether pharmacological intervention may be used to up-regulate sCR1 so as to inhibit complement in vivo should be further investigated. J. Leukoc. Biol. 65: 94–101; 1999.
T cell independence of bleomycin-induced pulmonary fibrosis
Authors: Helene M , Lake-Bullock V , Zhu J , Hao H , Cohen D A , Kaplan A M 
Published: January 2018

Abstract
The role of T cells and cytokines in bleomycin (BLM)-induced fibrosis was evaluated in susceptible and resistant strains of normal and SCID mice. Histology and hydroxyproline analysis showed that BLM induced pulmonary fibrosis in C57BL/6 and (C57BL/6 × BALB/c)F1 mice, whereas BALB/c mice were resistant to the disease. To test whether lymphocytes were required for the induction of BLM-induced pulmonary fibrosis, SCID mice were injected intratracheally with BLM and evaluated for the development of pulmonary inflammation and fibrosis. Similar morphological changes and increases in hydroxyproline were observed in both C57BL/6 SCID and (C57BL/6 × CB.17)F1 SCID animals compared to those seen in wild-type C57BL/6 and (C57BL/6 × BALB/c)F1 mice. In contrast, CB.17 SCID mice, which are genetically similar to BALB/c mice, were resistant to disease induction. Analysis of the cellular infiltrate in BLM-treated C57Bl/6 SCID mice confirmed a lack of T cells in the lungs of SCID mice and demonstrated a pronounced accumulation of eosinophils in areas of developing pulmonary fibrosis. NK cells were significantly elevated in untreated SCID mice and did not increase further after BLM treatment. Analysis of selected cytokines 1 day after initiation of BLM-induced pulmonary fibrosis indicated that the levels of TNF-α and IFN-γ appeared to segregate with fibrosis in both the SCID and wild-type mice. The data demonstrate that T cells are not required for the induction of fibrosis by BLM and suggest that responses by non-lymphoid cells may be sufficient for the induction of fibrosis. J. Leukoc. Biol. 65: 187–195; 1999.
Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils
Authors: Lundqvist-Gustafsson Helen , Bengtsson Torbjörn 
Published: January 2018

Abstract
Oxidative stress induces apoptosis in many types of cells, including human neutrophils. Our objective was to determine whether reactive oxygen species (ROS) produced by activated neutrophils are associated with accelerated apoptosis. Exposing neutrophils to ionomycin or phorbol myristate acetate (PMA) induced intracellular H2O2 production and rapid onset of apoptosis, measured as condensed chromatin, cellular shrinkage, and DNA fragmentation. Neutrophils activated with formyl-methionyl-leucyl-phenylalanine (fMLP) generated mainly extracellular H2O2 and did not undergo apoptosis. Exogenously added H2O2, together with the catalase blocker sodium azide, induced apoptosis to the same extent and with similar kinetics as PMA and ionomycin. Adenosine inhibited ionomycin-induced intracellular H2O2 production and apoptosis. Neither PMA nor ionomycin caused apoptosis in dimethyl sulfoxide-differentiated HL-60 cells, which are incapable of intracellular H2O2 production, whereas H2O2 induced apoptosis more efficiently in these cells than in neutrophils. We propose that activated neutrophils use intracellularly formed H2O2 to commit suicide. J. Leukoc. Biol. 65: 196–204; 1999.
Functions of Bruton's tyrosine kinase in mast and B cells
Authors: Kawakami Yuko , Kitaura Jiro , Hata Daisuke , Yao Libo , Kawakami Toshiaki 
Published: January 2018

Abstract
Bruton's tyrosine kinase (Btk) plays crucial roles in B cell differentiation as well as mast cell activation through the high-affinity IgE receptor (Fc∊RI). Defects in the btk gene lead to agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Mast cells from xid and btk null mice exhibit mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon Fc∊RI cross-linking. Recent studies demonstrated the role of Btk in a sustained increase in intracellular calcium concentrations in response to antigen receptor stimulation. Btk is also involved in the activation of stress-activated protein kinases, JNK/SAPK1/2, and thereby regulates c-Jun and other transcription factors that are important in cytokine gene activation. Regulation of the JNK/SAPK activation pathway by Btk may be related to the proapoptotic function of Btk in the programmed cell death in these hematopoietic cells. J. Leukoc. Biol. 65: 286–290; 1999.
Relationships between phosphatidic acid and cyclic nucleotide phosphodiesterases in activated human blood mononuclear cells
Authors: Zakaroff-Girard Alexia , Bawab Samer El , Némoz Georges , Lagarde Michel , Prigent Annie-France 
Published: January 2018

Abstract
We have previously shown that mitogenic activation of human PBMC rapidly increases both the intracellular phosphatidic acid (PA) level and cyclic nucleotide phosphodiesterase (PDE) activity, with time-course responses, suggesting a causative relationship between the two events. PA also directly stimulated cAMP-PDE activity in acellular systems. Thus the mitogenic properties of PA might be due to its ability to lower the level of cAMP, a negative effector of lymphocyte activation, through PDE activation. In this study, human PBMC were stimulated either with the mitogenic lectin ConA, the anti-CD3 mAb OKT3, or the phorbol ester TPA. All three agonists increased the radiolabeled PA level and the PA mass in treated cells and simultaneously increased cytosolic and particulate cAMP-and cGMP-PDE activities, with significant positive correlations between PA accumulation and PDE activities. Furthermore, the ConA-induced PDE activation was dose-dependently reduced by treatment of PBMC with the diacylglycerol-kinase inhibitor R59022. This compound also dose-dependently lowered the PA level and inhibited the proliferative response to ConA. In addition, TPA-induced PDE activation was totally abolished by ethanol, which strongly reduced PA accumulation in response to the phorbol ester. These data suggest that PA increase may be linked to mitogen-induced PDE activation. Experiments performed in the presence of rolipram indicated that ConA and TPA stimulated both the rolipram-sensitive PDE4 and the rolipram-insensitive PDE activities, OKT3 being more active on PDE4. All three agonists stimulated the cGMP-specific PDE5. These results suggest that PA is an important component of the mechanisms that maintain a low level of cyclic nucleotides, which is a prerequisite for an optimal lymphoproliferative response. J. Leukoc. Biol. 65: 381–390; 1999.
Functional roles of MCP-1 in Propionibacterium acnes-induced, T cell-mediated pulmonary granulomatosis in rabbits
Authors: Ichiyasu Hidenori , Suga Moritaka , Matsukawa Akihiro , lyonaga Kazuhiro , Mizobe Takanori , Takahashi Toshihiro , Ando Masayuki 
Published: January 2018

Abstract
The immunological manifestation of granuloma formations in humans largely depends on the delayed-type hypersensitivity response. We investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in a rabbit model of T cell-mediated pulmonary granulomatosis. Intravenous injection of Propionibacterium acnes (P. acnes) into sensitized rabbits induced massive and diffuse pulmonary granulomas. Levels of MCP-1 in sera and bronchoalveolar lavage fluids (BALF) peaked before the granuloma formation reached the peak (on days 1 and 3 after challenge, respectively). Chemotactic activities toward monocytes and T cells in BALF were inhibited by anti-MCP-1 IgG by 80 and 36%, respectively. The phenotypic analysis of the migrating T cells revealed that activated and memory T cells rather than naive cells were preferentially attracted to the BALF. Administration of anti-MCP-1 antiserum inhibited the development of granuloma formation in both size and number, the numbers of infiltrating leukocytes in BALF, the expression of adhesion molecules on peripheral monocytes/T cells, and on macrophages/T cells in BALF, and the production of TNF-α in the lung. Anti-MCP-1 resulted in a trend toward decreased level of IL-1β in the lung. The inhibition of the production of these cytokines appeared to be induced indirectly through the inhibition of the recruitment of macrophages that produce these cytokines. The results suggest important roles of MCP-1 in the development of granuloma formation in this model through the attraction and activation of specific types of cells. J. Leukoc. Biol. 65:482–491; 1999.
To die or not to die—the quest of the TRAIL receptors
Authors: Degli-Esposti Mariapia 
Published: January 2018

Abstract
The last 18 months have witnessed the characterization of several new members of the tumor necrosis factor (TNF) receptor family. Among these are five receptors for the cytotoxic ligand TRAIL (TNF-related apoptosis-inducing ligand). Two of these receptors, TRAIL-R1 and TRAIL-R2, contain classical cytoplasmic death domains and are able to transduce an apoptotic signal. The others lack functional death domains and are not able to promote cell death. Indeed, one of the receptors for TRAIL, osteoprotegerin (OPG) is a soluble protein whose activities so far have been shown to be inhibition of osteoclastogenesis and increased bone density in vivo. The existence of multiple receptors for TRAIL suggests an unexpected complexity to TRAIL-mediated biological functions. J. Leukoc. Biol. 65: 535–542; 1999.
Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation
Authors: Leino Lasse , Saarinen Kustaa , Kivistö Kaisa , Koulu Leena , Jansen Christer T , Punnonen Kari 
Published: January 2018

Abstract
We examined systemic effects of whole-body UVB irradiation on human peripheral blood phagocytes. We found that 24 h after a single erythemal dose of UVB radiation two phagocyte functions, adhesion and phagocytosis, were reduced by 50%. This functional suppression was accompanied by a significant decrease in the expression of complement receptors (CR1 and CR3) and IgG Fc receptors (FcRII and FcRIII). The greatest reduction (47%) was observed in CR3, which is important for both adhesion and phagocytosis. A kinetic analysis showed that both CR1 and CR3 levels started to decrease 15 min after the UVB exposure, reaching the lowest levels at 4.5- and 24-h time points, respectively. The down-modulation of CRs after whole-body UVB exposure was not due to a defective receptor synthesis or translocation from internal stores to plasma membrane because the maximal CR levels in stimulated cells were not affected by UVB. No change in the serum soluble ICAM-1 was detected after UVB, which rules out CD11b epitope masking by sICAM-1. UVB did not release low-receptor-density myeloid progenitor cells from storage pools into circulation. Interleukin 10, a mediator of UVB-induced immunosuppression, was unable to modulate CR expression in vitro. When seven suberythemal whole-body UVB exposures were given repeatedly within 2 weeks, a significant decrease in CR expression was seen, which was greatest after three irradiations. Our data suggest that an exposure to UVB has systemic effects in humans which, possibly due to the down-modulation of preexisting cell-surface receptors, suppress some important functions of circulating phagocytic cells. J. Leukoc. Biol. 65: 573–582; 1999.
Generation of CD28− cells from long-term-stimulated CD8+CD28+ T cells: a possible mechanism accounting for the increased number of CD8+CD28− T cells in HIV-1-infected patients
Authors: Fiorentini Simona , Malacarne Fabio , Ricotta Doris , Licenziati Stefano , Solis Adakatia Armenta , Ausenda Sabrina , De Francesco Maria , Garrafa Emirena , Simonini Andrea , Imberti Luisa , Balsari Andrea , Turano Adolfo , Caruso Arnaldo 
Published: January 2018

Abstract
According to CD28 molecule expression, CD8+ T cells can be classed as CD28bright, CD28dim, and CD28−. The CD28dim T cells were found to derive from mitogenic stimulated CD28− T cells but also from CD28bright T cells through a mechanism of CD28 down-modulation. Moreover, after prolonged in vitro interleukin-2 stimulation, clonal CD28bright cells showed a CD28dim expression before further evolution to a stable CD28− phenotype. This loss was concomitant with the disappearance of CD28 mRNA. A study of the cytokine production pattern revealed that CD28dim and CD28−T cell clones produced similar levels of type 1 and type 2 cytokines, which differed from those produced by the CD28bnght T cell clones. A high percentage of CD28dim and CD28− cells, with similarities in their cytokine production pattern, were found in the blood samples of HIV-infected patients, as compared to healthy donors. The CD28 down-modulation may account for the increased number of CD8+CD28− T cells in HIV-infected patients. J. Leukoc. Biol. 65: 641–648; 1999.
Increased neutrophil adherence and adhesion molecule mRNA expression in endothelial cells during selenium deficiency
Authors: Maddox Jane F , Aherne Kristen M , Reddy C Channa , Sordillo Lorraine M 
Published: January 2018

Abstract
Leukocyte aggregation and activation on endothelial cells (EC) are important preliminary events in leukocyte migration into tissue and subsequent inflammation. Thus, an increase in leukocyte adherence has the potential to affect inflammatory disease outcome. Selenium (Se) is an integral part of the antioxidant enzyme glutathione peroxidase (GSH-Px) and plays an important role in the maintenance of the redox state of a cell. Se supplementation in the bovine has been shown to improve the outcome of acute mastitis caused by coliform bacteria, in part by enhancing the speed of neutrophil migration into the affected mammary gland. However, the mechanisms by which Se modulates neutrophil migration have not been elucidated. Therefore, an in vitro model of Se deficiency in primary bovine mammary artery EC was used to examine the impact of Se status on the adhesive properties of EC. The effect of Se on functional activities was examined by measuring neutrophil adherence to Se-deficient and Se-supplemented EC. Se-deficient EC showed significantly enhanced neutrophil adherence when stimulated with tumor necrosis factor α (TNF-α) for 4 or 24 h, interleukin-1 for 12 h, or H2O2 for 20 min (P &lt; 0.05). To determine the mechanisms underlying these changes in neutrophil adherence, the expression of EC adhesion molecules, ICAM-1, E-selectin, and P-selectin were examined at the molecular level by a competitive reverse transcription-polymerase chain reaction. Results revealed higher mRNA expression for E-selectin and ICAM-1 in Se-deficient EC stimulated with TNF-α for 3 and 6 h, and greater expression of P-selectin mRNA in Se-supplemented EC with 3-h TNF-α stimulation. These studies provide new information to establish the role of Se nutrition in the initiation of leukocyte adherence to endothelium. J. Leukoc. Biol. 65: 658–664; 1999.