bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide production by peritoneal macrophages of Mycobacterium bovis BCG-infected or non-infected mice: regulatory roles of T lymphocytes and cytokines
Authors: Saito Shinji , Nakano Masayasu 
Published: January 2018

Abstract
Infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG) confers mice with strong abilities to produce nitric oxide (NO) and cytokines. Because the peritoneal macrophages taken from the mice immunized with live or heat-killed BCG can produce NO without any accessory cells and stimulants, it is difficult to clarify the immune regulation on NO production by manipulating the macrophages. Therefore, we investigated the participation of immune T cells and cytokines in NO production by using in vitro co-cultures of macrophages from non-immune mice with T cells prepared from BCG-infected mice in the presence or absence of a mycobacterial antigen, purified protein derivative (PPD). Although the non-immune thioglycollate (TGB)-elicited macrophages could not produce any detectable NO in the presence of PPD, supplementation of the macrophage cultures with CD4+ T cells prepared from BCG-infected mice enabled the macrophages to produce NO. Immunocytostaining showed that the macrophages, but not the immune T cells, expressed inducible NO synthase (iNOS), indicating that they were NO producers. PPD could only induce NO production if there was cell-cell contact of the CD4+ T cells in the immune cells and antigen-presenting macrophages were required for the NO production in response to PPD; this interaction led to the production of soluble mediators that induced NO production by the TGB macrophages. NO production by the co-cultured cells was abrogated by adding either anti-interferon-γ(IFN-γ) or anti-tumor necrosis factor α (TNF-α) antibody. Furthermore, the roles of immune T cells and PPD could be replaced by adding recombinant IFN-γ together with TNF-α to the macrophage cultures, but neither alone was sufficient to induce NO production by the macrophages. Our present data indicate that TNF-α produced by PPD-stimulated macrophages and IFN-γ produced by cell-cell interaction of BCG-immune T cells and antigen-engulfed macrophages together activate the macrophages to produce NO.
Recombinant natural killer enhancing factor augments natural killer cytotoxicity
Authors: Sauri Humberto , Ashjian Peter H , Kim Anthony T , Shau Hungyi 
Published: January 2018

Abstract
Natural killer enhancing factor (NKEF) was originally identified and studied because of its ability to enhance NK cytotoxicity in vitro. After cloning the two genes responsible for NKEF proteins, NKEF-A and -B, we found that they belong to a newly described and highly conserved antioxidant gene family. We have now produced recombinant proteins of both genes and used them to test for their ability to promote NK cytotoxicity. Although recombinant NKEF (rNKEF)-A and -B have similar levels of antioxidant function, only the reduced form of rNKEF-A can enhance NK cytotoxicity. These results indicate that both the antioxidant and NK-enhancing functions of rNKEF-A and -B probably involve the cysteine residues of the proteins but are mediated by separate domains of the molecules. We pretreated both effector cells and target cells to investigate which population was influenced by rNKEF-A, and determined that the protein must be present during the cytotoxicity assay to enhance the activity. Despite the similarities between NK cytotoxicity and lymphokine-activated killer (LAK) cytotoxicity, rNKEF-A is not effective in augmenting LAK cytotoxicity. Therefore, rNKEFs can be useful tools in not only protecting cells from oxidative damage, but also in selectively promoting NK cytotoxicity against certain tumor cells.
Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells
Authors: Ichiki A T , Gibson L A , Jago T L , Strickland K M , Johnson D L , Lange R D , Allebban Z 
Published: January 2018

Abstract
The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to microgravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.
Apoptotic cell death in activated monocytes following incorporation of clodronate-liposomes
Authors: Schmidt-Weber Carsten B , Rittig Michael , Buchner Eberhard , Hauser Ingeborg , Schmidt Irina , Palombo-Kinne Ernesta , Emmrich Frank , Kinne Raimund W 
Published: January 2018

Abstract
The present study was performed to elucidate whether sterically stabilized liposomes laden with clodronate, which lead to depletion of macrophages (Mɸs) and amelioration of experimental autoimmune arthritis in vivo, selectively affect cells of the mɸ lineage in vitro. The rates of incorporation of drug-free, fluorescent liposomes and the rates of cell death following exposure to clodronate-liposomes were assessed in human peripheral blood monocytes, as well as in polymorphonuclear leukocytes (PMNs), T cells, endothelial cells, and fibroblasts, both at rest and following activation. Gel electrophoresis of nuclear extracts and ultrastructural analyses were performed to identify the modality of cell death. Monocytes, particularly upon activation, were more efficient in incorporating sterically stabilized liposomes than all other cells except PMNs. Twenty percent of resting monocytes and up to 65% of activated monocytes died within 24 h of exposure to clodronate-liposomes, whereas the other cell types, including PMNs, remained unaffected. Activated monocytes exposed to clodronate-liposomes, but not resting or activated monocytes exposed to drug-free liposomes, showed clear signs of apoptotic cell death. In most of the assays, sterically stabilized liposomes were more efficient than conventional phosphatidylcholine-liposomes. Sterically stabilized clodronate-liposomes preferentially affect cells of the mɸ lineage, particularly if activated. Selective elimination of activated Mɸs by apoptosis may explain both therapeutic efficacy and safety of clodronate-liposomes in experimental models of autoimmunity.
Cloning of the murine eosinophil peroxidase gene (mEPO): characterization of a conserved subgroup of mammalian hematopoietic peroxidases
Authors: Horton Margaret A , Larson Kirsten A , Lee James J , Lee Nancy A 
Published: January 2018

Abstract
The mouse eosinophil peroxidase (mEPO) gene was cloned by screening a random-primed bone marrow cDNA library at reduced criteria using a hEPO cDNA. An mEPO cDNA was subsequently used to isolate the mEPO gene from a λ-genomic library. The mEPO gene displays a high degree of conservation with its human homologue: the transcription units are approximately the same size, conserve the relative size and position of the 12 exons associated with each gene, and at a nucleotide level the mouse and human EPO genes are 86% identical in the protein coding regions and 66% identical in the 3'-untranslated trailer regions. This strong conservation extends to the encoded proteins which show ~90% amino acid identity. Expression of the mEPO gene is restricted to tissues containing eosinophil progenitor cells (e.g., bone marrow and spleen), a pattern similar to the expression of another murine eosinophil granule protein, major basic protein.
HIN-200: a novel family of IFN-inducible nuclear proteins expressed in leukocytes
Authors: Dawson Michelle J , Trapani Joseph A 
Published: January 2018

Abstract
In recent years a novel family of Interferon (IFN)-inducible nuclear proteins has been identified in both mouse and humans and implicated in the control of myeloid differentiation. Recent evidence suggests that this role may be mediated by an effect on cell cycle regulation through interaction with known transcriptional regulators. Our laboratory first identified a nuclear protein designated IFI 16, which is strongly inducible with IFN-α and -γ in myeloid cells. IFI 16 shares homology with at least six IFN-inducible mouse genes, designated the Gene 200 cluster, and also has close similarity with the human myeloid cell nuclear differentiation antigen, whose expression has also been associated with later stages of normal myelopoiesis and some myeloid malignancies. The structural hallmark of each protein in this family of hemopoietic IFN-inducible nuclear proteins is a 200-amino acid motif (hence HIN-200), present singly or as a tandem repeat. The restricted expression of these proteins, their ability to bind to nucleic acid, and their expression in response to a variety of stimuli eliciting myeloid differentiation strongly suggest that they play a role in hemopoietic maturation.
Migration of rat skin dendritic cells
Authors: Richters C D , van Pelt A M , van Geldrop E , Hoekstra M J , van Baare J , du Pont J S , Kamperdijk E W A 
Published: January 2018

Abstract
This study examines the in vivo migration of rat skin dendritic cells (including Langerhans cells) after skin transplantation. As donor animals, PVG-RT7b rats were used. The leukocytes of these rats bear an epitope of the leukocyte common antigen that can be recognized by use of the antibody His 41. The cells of allogeneic (ACI) recipient strains do not label with this antibody. Four days after transplantation of PVG-RT7b skin on allogeneic recipients, His 41+ cells showing a dendritic morphology were present in the T cell area of the draining lymph nodes. During culture of rat skin explants, dendritic cells migrated spontaneously into the medium. These in vitro migrated cells showed a high capacity to stimulate allogeneic T cells. When these cells, obtained from PVG-RT7b skin, were injected into the hind footpads of allogeneic recipients, they migrated to the same compartments of the draining lymph node. These data indicate that the cells that migrate from a transplanted allogeneic skin graft are the same cells that migrate in vitro from explants. Most probably, they initiate graft rejection in the draining lymph nodes of the recipient.
Liposome-encapsulated dichloromethylene diphosphonate induces macrophage apoptosis in vivo and in vitro
Authors: Naito Makoto , Nagai Hirotaka , Kawano Sunao , Umezu Hajime , Zhu Hong , Moriyama Hiroshi , Yamamoto Takashi , Takatsuka Hisakazu , Takei Yoshiyuki 
Published: January 2018

Abstract
Dichloromethylene diphosphonate (MDPCl2) encapsulated in multilamellar liposomes was selectively incorporated by macrophages, immediately transferred to lysosomes, then released from liposomes into lysosomes by enzymatic digestion of the liposomal lipid layers. From 4 h after ingesting liposome-encapsulated MDPCl2 murine macrophages in vivo and in vitro acquired the ultrastructural features of apoptosis, such as condensed nuclear chromatin, nuclear fragmentation, cell shrinkage, and blebbing of the plasma membrane. Murine peritoneal macrophages and isolated rat Kupffer cells incubated in the medium containing liposome-encapsulated MDPCl2 increased DNA fragmentation in a dose-dependent manner. Electrophoretic analysis of extracted DNA from the isolated Kupffer cells showed DNA fragmentation. Another diphosphonate, Alendronate (4-amino-1-hydroxybutylidene-1,1-diphosphonate) had less potent macrophage cytotoxicity. However, MDPCl2, Alendronate, and gadolinium chloride in solution were not cytotoxic to macrophages. These results implied that the intralysosomal accumulation of MDPCl2 generates signals to induce macrophage apoptosis.
Signaling by IL-2 and related cytokines: JAKs, STATs, and relationship to immunodeficiency
Authors: Johnston James A , Bacon Chris M , Riedy M C , O'Shea John J 
Published: January 2018

Abstract
Cytokines that bind to the interleukin-2 (IL-2) receptor common gamma chain (γc), including IL-2, IL-4, IL-7, IL-9, and IL-15, are important for the growth and differentiation of T and B lymphocytes, natural killer cells, macrophages, and monoctyes. These cytokines have overlapping biological effects that in part result from the use of the shared receptor subunit γc. Recently it has become clear that these cytokines activate a number of important intracellular signaling molecules, including the Janus kinases JAK1 and JAK3 and members of the transcription factor family of signal transducers and activators of transcription (STATs). The discovery of these signaling pathways has led to important new insights into their role in lymphocyte maturation, as it has emerged that mutations in the genes encoding both γc and JAK3 result in similar forms of severe combined immunodeficiency (SCID). In this review we examine the structure and function of cytokine receptors and the signaling pathways involved in their regulation of gene expression. Furthermore, we discuss recent advances that have led to a better understanding of how cytokines elicit intracellular responses, as well as their role in normal lymphoid development.
Elevated TNF-α and inducible nitric oxide production by alveolar macrophages after exposure to a nitrite inhalant
Authors: Soderberg Lee S F , Chang Louis W , Barnett John B 
Published: January 2018

Abstract
Abuse of nitrite inhalants, widespread among male homosexuals, has been identified by epidemiological studies as an independent risk factor for AIDS and for Kaposi's sarcoma. Subchronic exposure of mice to inhaled isobutyl nitrite was previously found to impair the tumoricidal activity of peritoneal macrophages. Because inhalants would be expected to have the greatest effects on cells in the lung, alveolar macrophages from exposed mice were examined in this study. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 min/day for 14 days. Following this treatment, the lungs of exposed mice had large increases in ccllularity, both in the alveolar septa and within the alveoli. Broncho alveolar lavages also contained increased numbers of cells. Alveolar macrophages collected from treated mice had increased tumoricidal activity compared with controls and produced higher levels of inducible nitric oxide and tumor necrosis factor-α (TNF-α), The frequency of alveolar cells secreting TNF-α was increased ninefold in mice exposed to the inhalant. Cell influx into the lung, as indicated by the presence of red blood cells in lung lavages, was evident after only a single 45-min exposure to inhaled isobutyl nitrite at doses as low as 300 ppm.
Gadolinium chloride inhibits Kupffer cell nitric oxide synthase (iNOS) induction
Authors: Roland Claude R , Naziruddin Bashoo , Mohanakumar T , Flye M Wayne 
Published: January 2018

Abstract
Kupffer cells (KC) are the phagocytic macrophages of the liver. The rare earth metal, gadolinium (GdCl3), is a lanthanide, which, after phagocytosis by the KC, has been found to alter various aspects of KC physiology. In this study, we describe for the first time that the in vivo administration of GdCl3 to rate decreases the release of NO by isolated rat KC in response to lipopolysaccharide. Western blot analysis shows decreased expression of both imlucible nitric oxide synthase as well as total cellular calmodulin after GdCl3 treatment. Possible mechanisms for this phenomenon are suggested.
Regulation of cytokine and cytokine receptor expression by glucocorticoids
Authors: Almawi Wassim Y , Beyhum Hayfa N , Rahme Amal A , Rieder Michael J 
Published: January 2018

Abstract
Glucocorticoids (GCS) profoundly inhibit several aspects of T cell immunity largely through inhibition of cytokine expression at the transcriptional and posttranscriptional levels. GCS were also reported to act indirectly by inducing transforming growth factor-β expression, which in turn blocks T cell immunity. In exerting their antiproliferative effects, GCS diffuse into target cells where they bind their cytoplasmic receptor, which in turn translocates to the nucleus where it inhibits transcription of cytokine genes through direct binding to the glucocorticoid response elements (GRE), which are located in the promoter region of cytokine genes or, alternatively, through antagonism of the action of transcription factors required for optimal transcriptional activation. In contrast to their inhibitory effects on cytokine expression, GCS upregulate cytokine receptor expression that correlates with enhanced cytokine effects on target cells. In this review, we summarize the current state of knowledge of the mechanism of action of GCS, including the phenomenon of steroid-induced rebound, which ensues upon GCS withdrawal.
Requirement for CD44 in proliferation and homing of hematopoietic precursor cells
Authors: Khaldoyanidi Sophia , Denzel Angela , Zöller Margot 
Published: January 2018

Abstract
The hematopoietic form of the adhesion molecule CD44 is known to be involved in lymphocyte maturation and homing. To define lineage and stage of maturation, which requires expression of CD44, murine long-term bone marrow cultures were established. Stroma formation and proliferation of early as well as committed erythroid, myeloid, and lymphoid progenitors were evaluated under the influence of monoclonal anti-CD44 antibodies. Although the formation of stromal elements was not affected, formation of cobblestone areas was completely abolished. [3H]thymidine suicide confirmed that anti-CD44 treatment interfered with the proliferation of early and committed hematopoietic progenitor cells. In addition, homing and seeding of bone marrow cells was impaired by anti-CD44. The data are indicative of a dual functional mode of CD44 in adhesion and proliferation of hematopoietic progenitors and confirm an essential requirement for the molecule in early stages of hematopoiesis.
N-acetyl-L-cysteine-induced up-regulation of HIV-1 gene expression in monocyte-derived macrophages correlates with increased NF-κB DNA binding activity
Authors: Nottet Hans S L M , Moelans Inge I M D , de Vos N Machiel , de Graaf Loek , Visser Maarten R , Verhoef Jan 
Published: January 2018

Abstract
Nuclear factor κB (NF-κB) is an important cellular regulator of human immunodeficiency virus (HIV) gene expression. In T cells, N-acetyl-l-cysteine (NAC) inhibits the induction of NF-κB and transcription of HIV-1. However, NAC up-regulates HIV-1 replication in monocyte-derived macrophages (MDM). In this study we demonstrate that NAC treatment of MDM transfected with a chloramphenicol acetyltransferase (CAT) construct under transcriptional control of the HIV-1 long terminal repeat resulted in an up-regulation of CAT activity. Furthermore, MDM transfected with a HIV-1-NF-κB-CAT construct also produced increased CAT activity after NAC treatment. In addition, electrophoretic mobility shift assays revealed that nuclei of NAC-treated MDM contained increased binding activity to wild-type, but not mutant, κB oligonucleotides. Components of the binding activity were identified with antibodies as the NF-κB subunits p50 and p65. These data indicate that NAC-induced enhancement of HTV-1 replication in MDM is regulated at the level of viral gene expression and mediated by NF-κB.
Immunoreceptor tyrosine-based activation motif (ITAM), a unique module linking antigen and Fc receptors to their signaling cascades
Authors: Isakov Noah 
Published: January 2018

Abstract
Signal transduction by the T cell and B cell antigen receptors and by receptors for a variety of immunoglobulins' Fc region is strictly dependent on a receptor subunit cytoplasmic module termed immunoreceptor tyrosine-based activation motif (FE4M). Hris module exists in one or more copies in each of the receptor-associated signal-transducing molecules and it possesses two repeats of the consensus sequence Tyr-X-X-Leu/IIe spaced by six to eight amino acids. Receptor engagement is followed by a rapid and transient phosphorylation of tyrosine residues within their ITAMs, thereby creating temporary binding sites for Src homology 2 (SH2)-containing signaling molecules operating downstream of the activated receptor. The purpose of this review is to discuss recent findings on the functional role of ITAMs in antigen and Fc receptor-mediated signal transduction, with a particular emphasis on kinases operating upstream and downstream of the ITAMs.
Enhancement of immune response to naked DNA vaccine by immunization with transfected dendritic cells
Authors: Manickan Eianchezhiyan , Kanangat Sivadasan , Rouse Richard J D , Yu Zhiya , Rouse Barry T 
Published: January 2018

Abstract
Immunization with plasmid DNA encoding various proteins promises to be a valuable vaccine approach especially if its immunogenicity could be optimized. In this study we show that the intramuscular delivery in dendritic cells (DC) of naked plasmid DNA encoding two proteins of herpes simplex virus (HSV) leads to the induction of significantly enhanced levels of resistance to viral challenge. Whereas DC transfected in vitro with DNA induced enhanced immunity, similarly transfected macrophage (Mɸ) populations lacked immunogenicity even though plasmid expression occurred in vitro. The enhanced immunity induced by DC-delivered DNA appeared to be associated mainly with an increased Thl CD4+ T cell response. Our results add evidence that DC are the essential antigen-presenting cell types involved in immune responses to intramuscularly administered DNA vaccines.
γδ T cell activation or anergy during infections: the role of nonpeptidic TCR ligands and HLA class I molecules
Authors: Poccia Fabrizio , Malkovsky Miroslav , Gougeon Marie Lise , Bonneville Marc , Lopez-Botet Miguel , Fournié Jean Jacques , Colizzi Vittorio 
Published: January 2018

Abstract
Vγ9Vδ2-encoded T cell receptors (TCR) expressed by most human peripheral blood γδ T cells mediate the recognition of nonpeptidic phosphoantigens from various pathogens without any known requirement for HLA molecules. Functionally mature Vγ9Vδ2 T cells display a potent natural killer (NK) -like cytotoxic activity, share with NK cells the expression of inhibitory receptors for HLA class I molecules, and release a plethora of cytokines, most notably interferon-γ and tumor necrosis factor α. Hence, through local activation, the early recruitment and stimulation of Vγ9Vδ2 T cells may promote efficient anti-infectious immunity. However, a chronic overactivation of this T cell subset may result in immunopathology. The meeting held in St. Vincent, Val d'Aosta, Italy (symposium on γδ T cells in natural immunity to infections: a rationale for vaccine development organized by the World Foundation for AIDS Research and Prevention, the UNESCO, and the Italian National Research Council, December 2–4, 1996) focused on the importance of γδ T cell activation and anergy for the pathogenesis of tuberculosis, malaria, and HIV infections.