bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of hepatic endothelial cell and macrophage proliferation and nitric oxide production by GM-CSF, M-CSF, and IL-1β following acute endotoxemia
Authors: Feder Lisa S , Laskin Debra L 
Published: January 2018

Abstract
Treatment of rats with bacterially derived lipopolysaccharide (LPS), a condition that mimics acute endotoxemia, results in a significant increase in the number of endothelial cells and macrophages in the liver. This is correlated with the release of proinflammatory and cytotoxic mediators that induce liver damage. In the present studies, we analyzed the effects of various inflammatory mediators released during the pathogenesis of hepatic injury on proliferation of liver nonparenchymal cells. To induce acute endotoxemia female Sprague-Dawley rats were injected intravenously with 5 mg/kg LPS. Endothelial cells and macrophages were isolated 48 h later by combined collagenase and pronase perfusion of the liver followed by centrifugal elutriation. Interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) had no effect on proliferation of either endothelial cells or macrophages. In contrast, whereas interleukin-1β (IL-1β) inhibited the proliferation of endothelial cells from untreated rats, this cytokine stimulated the growth of cells from endotoxemic rats. The colony-stimulating factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-GSF), also markedly enhanced the proliferation of endothelial cells, as well as macrophages from endotoxemic rats. Macrophages from endotoxemic rats were more sensitive to the colony-stimulating factors than cells from untreated rats. In contrast, the inflammatory mediators LPS and interferon-γ (IFN-γ) inhibited endothelial cell and macrophage growth, an effect that was partially blocked in endothelial cells by the nitric oxide synthase inhibitor NG-monomethyl-l-aiginine (L-NMMA). This suggests that growth inhibition in these cells is mediated, in part, by nitric oxide. Interestingly, in both endothelial cells and macrophages from endotoxemic rats, GM-CSF, M-CSF, and IL-1β synergized with LPS and IFN-γ to induce nitric oxide production. This was correlated with a further inhibition of proliferation that was partially reversed by L-NMMA in endothelial cells but not macrophages. Taken together these data demonstrate that endothelial cell and macrophage proliferation in the liver is controlled by a variety of mediators released during endotoxemia; however, the mechanisms regulating growth in the two cell types are distinct. J. Leukoc. Biol. 55: 507–513; 1994.
Use of the 5′ -flanking region of the mouse perforin gene to express human Fcγ receptor I in cytotoxic T lymphocytes
Authors: Smyth Mark J , Kershaw Michael H , Hulett Mark D , McKenzie Ian F C , Trapani Joseph A 
Published: January 2018

Abstract
Expression of the gene encoding the cytolytic granule protein perforin is restricted to cytotoxic lymphocytes. To undertake a functional analysis of the immediate 5′-promoter region of the mouse perforin gene, we transiently transfected mouse perforin promoter-chloramphenicol acetyltransferase (CAT) reporter gene constructs into cytotoxic T, T lymphoid, B-lymphoid, and nonlymphoid cell lines. The transcriptional activity of the perforin promoter was restricted to cytotoxic lymphocytes. The perforin promoter was controlled by several positive (in perforin-positive cells) and negative (in perforin-negative cells) cis-acting regions, spread over at least 1.1 kilobases. The most specific expression of the CAT reporter gene in the interleukin-2-dependent cytotoxic T cell line CTLL-R8 was obtained with the mouse perforin promoter encompassing positions -1104 to +1 in relation to the RNA cap site. This construct expressed 65- to 70-fold higher CAT activity than the promoterless CAT construct in perforin-expressing cells but only 1- to 5-fold higher CAT activity than the promoterless construct in nonlymphoid cells. On the basis of these data, we used this most specifically active mouse perforin promoter, -1104 to +1, to express in CTLL-R8, a chimeric human receptor comprising the extracellular domains of human FcγRI and the transmembrane and intracellular domains of TCR . Selection in G418-containing medium produced CTLL-R8 transfectant clones that (1) expressed high levels of human FcγRI mRNA; (2) expressed cell surface FcγRI as demonstrated by immunoprecipitation and their ability to bind the Fc portion of human and mouse monoclonal antibodies (mAbs) in an isotype-specific manner, and (3) bound RBC expressing mucin-1 (Muc-1) peptide in the presence of a chimeric mouse-human anti-Muc-1 mAb. Activation of CTLL-R8 transfectants upon engagement of the human FcγRI was evidenced by their ability to lyse tumor target cells in an mAb isotype-dependent manner. The successful expression of a functional chimeric gene in CTLL-R8 suggests that the mouse perforin promoter represents a novel reagent for expressing exogenous genes in cytotoxic T lymphocytes. J. Leukoc. Biol. 55: 514–522; 1994.
Gestation-related expression of the interferon-γ receptor gene in mouse uterine and embryonic hematopoietic cells
Authors: Chen Hua-Lin , Kamath Ravi , Pace Judith L , Russell Stephen W , Hunt Joan S 
Published: January 2018

Abstract
Macrophages and natural killer (NK)–like cells are the major hematopoietic cell populations in the cycling and pregnant mouse uterus and are also found in the embryo. In order to evaluate potential receptivity of these cells to interferon-γ (IFN-γ), tissues taken from cycling and pregnant mice were tested for IFN-γ receptor (IFN-γR) mRNA and protein. Macrophages were identified immunohistochemically by using the specific monoclonal antibody F4/80. NK cells were identified by their large size, distinctive intracellular granules, and binding of a monoclonal antibody to the common leukocyte antigen. In cycling uteri, the abundance of IFN-γR mRNA relative to an invariant message (glyceraldehyde-3-phosphate dehydrogenase) increased during progression of the hormonally regulated estrous cycle. IFN-γR mRNA in situ hybridization signals were slightly higher in macrophage-like than in other types of endometrial stromal cells. In pregnant uteri, the highest proportions of IFN-γR mRNA were observed at gestation day (g.d.) 16. Specific message and protein were present in uterine macrophages by g.d. 7 and in NK cells by g.d. 9. IFN-γR expression in both lineages remained stable through the balance of pregnancy. In embryos, IFN-γR mRNA increased between g.d. 14 and 16. Specific transcripts were present in many cells at g.d. 14, but none were detected in embryonic liver macrophages until g.d. 16. The results of this study suggest relationships between IFN-γR expression and ovarian hormones as well as cell maturation and support the postulate that IFN-γ receptor-ligand interactions may improve the ability of uterine and embryonic hematopoietic cells to perform specific tasks during gestation. J. Leukoc. Biol. 55: 617–625; 1994.
Cytokines and tuberculosis
Authors: Wallis Robert S , Ellnor Jerrold J 
Published: January 2018

Abstract
The evolution of Mycobacterium tuberculosis as an intracellular pathogen has led to a complex relationship between it and its host, the human mononuclear phagocyte. The products of M. tuberculosis–specific T lymphocytes are essential for macrophage activation for intracellular mycobacterial killing. However, some cytokines, including products of both lymphocytes and phagocytic cells, may contribute to enhanced mycobacterial survival and replication. In human immunodeficiency virus-associated tuberculosis, cytokine products may mediate enhanced susceptibility to tuberculosis as well as accelerated progression to AIDS. Better understanding of these interactions will allow the development of increasingly specific immune-based interventions for prevention and treatment of tuberculosis. J. Leukoc. Biol. 55: 676–681; 1994.
Temporal down-regulation of FcγRIII expression and Fcγ receptor-mediated phagocytosis in human monocyte-derived macrophages induced by TNF-α and IL-1β
Authors: Liao Guojuan , Simon Sanford R 
Published: January 2018

Abstract
Effects of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) on the expression of Fcγ receptors (FcγRs) and on FcγR-mediated phagocytosis in human monocyte-derived macrophages (MDMs) have been determined. Treatment of MDMs with TNF-a (400 pg/ml) or IL-1β (400 pg/ml) for 80 min decreased cell surface FcγRIII expression, as measured by flow cytometry (FAGS), while the levels of surface FcγRI and FcγRII remained unchanged. Surface FcγRIII expression remained depressed for 7 h after exposure of MDMs to either cytokine but then rose progressively until, by 24 h of stimulation, the levels were at least as high as those on unstimulated cells. In parallel with cell surface FcγRII I levels, phagocytosis of immunoglobulin G-opsonized fluorescent beads, as measured by FAGS, decreased and then increased over time after stimulation of MDMs with TNF-α while the opsonin-independent phagocytic activity was unchanged, suggesting that among the three classes of Fcγ receptors on macrophages, FcγRIII may play a critical role in regulating opsonic phagocytosis. After treatment with IL-1β, both opsonic and nonopsonic phagocytic activities of MDMs were significantly decreased, regardless of FcγRIII levels. FAGS analysis of rhodamine-phalloidin-stained MDMs showed that after incubation with IL-1β, but not TNF-α, the content of Factin declined in MDMs, coinciding with inhibition of particle phagocytosis. Rapid down-regulation and subsequent recovery of macrophage FcγRIII expression following cytokine stimulation could serve as a novel regulatory mechanism employed by inflammatory cells in host defensc. J. Leukoc. Biol. 55: 702–710; 1994.
Synthetic polysulfated hyaluronic acid is a potent inhibitor for tumor necrosis factor production
Authors: Chang Nan-Shan , Intrieri Catherine , Mattison Jeffery , Armand Gerard 
Published: January 2018

Abstract
Based on the premise that naturally occurring glycosaminoglycans could serve as building blocks for synthesizing nontoxic drugs for suppression of tumor necrosis factor (TNF) production by inflammatory cells, we have chemically modified hyaluronic acid (HA) and tested its effects in blocking TNF-α and TNF-β production in vitro. HA was chosen mainly for its structural simplicity, nonimmunogenicity, and readiness for chemical modifications. When HA was chemically polysulfated to a sulfate/hexosamine molar ratio of 3.9, the sulfated HA, was shown to be a potent inhibitor of TNF-α production in lipopolysaccharide (LPS)- or interferon-γ-activated THP-1 cells. For example, a concentration of HAs as low as 10 ng/ml reduced TNF-α production in LPS-activated THP-1 cells more than 50%, whereas achieving a similar extent of reduction required 50 μg/ml native HA. By decreasing the extent of polysulfation, the inhibitory effect of HAS on TNF-α production was diminished. Other chemical modifications, including deacetylation, thiolation, or reduction of the carboxylic groups, could not increase the efficacy of HA in suppression of TNF-α production. Naturally polysulfated glycosaminoglycans, such as chondroitin sulfates, keratan sulfate, heparan sulfate, and heparin, failed to inhibit TNF-α production. HA, also restricted TNF-β (lymphotoxin) secretion in an Epstein-Barr virus-transformed B cell line, Roha-9, which constitutively produces TNF-β. HA, had no inhibitory effect on the proliferation of THP-1 or Roha-9 cells, which would account for the reduced TNF-α or TNF-β production. Furthermore, time-course metabolic labeling studies revealed that HA, could not restrict overall protein synthesis and secretion in THP-1 cells. However, HA, increased complement Clq secretion in THP-1 in a dose-dependent manner, but it had no effect on biosynthesis of complement Cl inhibitor, factor D, and Fcγ receptor type II (FcγRII). These results indicate that HA, selectively restricts the production of TNF-α, TNF-SbT, and probably several other protein species. J. Leukoc. Biol. 55: 778–784; 1994.
Cytokine induction of granule protein synthesis in an eosinophil-inducible human myeloid cell line, AML14
Authors: Paul Cassandra C , Ackerman Steven J , Mahrer Susan , Tolbert Marshall , Dvorak Ann M , Baumann Michael A 
Published: January 2018

Abstract
Study of eosinophil growth and differentiation has been hampered by the difficulty of obtaining adequate numbers of highly purified eosinophil progenitors or mature eosinophils for analysis. The AML14 myeloid leukemia cell line has the unusual ability to exhibit eosinophilic differentiation in response to stimulation by combinations of the eosinophil-active cytokines interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and IL-5. We now demonstrate that AML14 cells can be stimulated by a combination of these cytokines to produce mRNA encoding all the eosinophil granule proteins, including major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and the Charcot-Leyden crystal (CLC) protein (eosinophil lysophospholipase). The production of the mature proteins was demonstrated by Western blotting, and ultrastructural analysis demonstrated the presence of immature secondary granules in cells that had been induced to differentiate to eosinophils. These findings demonstrate the utility of the AML14 cell line as a model for the study of cytokine induction of eosinophil growth and differentiation. J. Leukoc. Biol. 56: 74–79; 1994.
Role of diradylglycerol formation in H2O2 and lactoferrin release in adherent human polymorphonuclear leukocytes
Authors: Nakamura Tadashi , Suchard Suzanne J , Abe Akira , Shayman James A , Boxer Laurence A 
Published: January 2018

Abstract
Polymorphonuclear leukocytes (PMNs) adherent to fibrinogen exhibit a delay in the release of H2O2 in response to fMLP. Previously, we demonstrated that H2O2 release in adherent PMNs coincides with the exocytosis of lactoferrin-containing specific granules and activation of phospholipase D (PLD). We also found that chelation of intracellular calcium blocked both lactoferrin and H2O2 release in stimulated PMNs in spite of the fact that adhesion and spreading remained normal. Since diradylglycerol (DRG) formation has been implicated in PMN secretion and oxidant release, we determined the effect of intracellular calcium chelation on PLD activation and DRG formation to ascertain whether DRG formation was coupled to lactoferrin and H2O2 release. We observed that chelation of intracellular calcium with bis-(O-aminophenoxy)-ethanol-N,N;N'- tetraacetic add (BAPTA) prevented PLD activation as monitored by inhibition of phosphatidylethanol formation. Formation of DRG derived from phosphatidic acid (PA) was also inhibited in the presence of BAPTA. Following the addition of the calcium ionophore ionomycin to the BAPTA-treated PMNs, lactoferrin and H2O2 release was coincident with the onset of DRG formation. Also the addition of sn-1,2-didecanoylglycerol to the BAPTA-treated PMNs stimulated them to release H2O2. Our studies support the hypothesis that DRG derived from PLD activation is required for degranulation of specific granules and associated H2O2 release from adherent PMNs. J. Leukoc. Biol. 56: 105–109; 1994.
Use of suicide genes in gene therapy
Authors: Tiberghien Pierre 
Published: January 2018

Abstract
Gene therapy encompasses a broad range of treatment modalities that may eventually be applied to a variety of genetic as well as acquired diseases. In addition to compensating for a defective gene—and enhancing a cellular function—gene transfer can allow for a conditional negative selection of target cells. Indeed, the transfer of a gene encoding a susceptibility factor can make a cell specifically sensitive to a drug. After genomic integration, such a potentially destructive gene is endogenously expressed and has therefore been coined a suicide gene. This review describes current experimental approaches and prospects for using suicide genes for the treatment of human diseases. J. Leukoc. Biol. 56: 203–209; 1994.
Sulfated polyanions prevent HIV infection of lymphocytes by disruption of the CD4-gp120 interaction, but do not inhibit monocyte infection
Authors: Lynch G , Low L , Li S , Sloane A , Adams S , Parish C , Kemp B , Cunningham A L 
Published: January 2018

Abstract
Sulfated polyanions (SPs) bind variably to lymphocyte-expressed CD4 and inhibit binding of monoclonal antibodies to the first two domains of CD4. To further define this interaction, soluble recombinant CD4 (sCD4; four extracellular domains), its truncated amino-terminal two-domain derivative, and three linear peptide analogues spanning residues 6–60 (6–24, 20–40, 41–60) in the first domain were investigated for SP binding. Dextran sulfate (DXS) (500 kDa), polyvinyl sulfate, fucoidan, and carrageenan-kappa, each immobilized on carboxymethyl cellulose fibers, bound strongly to both the two-domain and four-domain recombinant CD4 molecules (similar to that observed with native CD4), whereas dextran sulfate (5 kDa), chondroitin 6-sulfate, and pentosan sulfate bound relatively poorly. No peptide binding to SPs was observed. Recombinant gp120 bound poorly (&lt;10%) to all of the immobilized polyanions, except pentosan sulfate (17%), for which some binding was noted. Binding of radiolabeled V3 loop peptide to SPs was slightly greater, with 20-30% binding to polyvinyl sulfate, dextran sulfate (500 kDa), and pentosan sulfate. Competitive binding studies demonstrated the predominance of sCD4 rather than rgp120 binding to SPs and supported previous data demonstrating a binding site for DXS (500 kDa) on the first domain of CD4 adjacent to the gp120 binding site and recognized by OKT4C and E monoclonal antibodies. Hence disruption of the CD4-gp120 interaction is probably responsible for most of the observed antiviral activity of SPs toward HIV infection of lymphocytes. However, HIV infection and gp120 binding to monocytes was unaffected by SPs, probably because SPs were unable to block the CD4-gp 120 interaction in monocytes. J. Leukoc. Biol. 56: 266–272; 1994.
Expression of CD11/CD18 and ICAM-1 on monocytes and lymphocytes of HIV-1-infected individuals
Authors: Stent Gianna , Cameron Paul U , Crowe Suzanne M 
Published: January 2018

Abstract
The role of the leukocyte integrins in the infection of cells by HIV-1 or in the progression of AIDS-related disease is of continuing interest. Using a duallabeling flow cytometric method, we determined the level of expression of the leukocyte integrins and intercellular adhesion molecule 1 (ICAM-1) on monocytes and lymphocytes from HIV-1-infected and uninfected individuals. The mean fluorescence of CD18 on lymphocytes and CD11c on monocytes of HIV-1-infected subjects was significantly higher than for the control group (P=.008 and.014, respectively). There was a trend toward higher fluorescence of CD11a on lymphocytes from HIV-1-infected subjects compared with cells from the control group (P=.089). Integrin expression on lymphocytes or monocytes from HIV-infected individuals did not correlate with their CD4 lymphocyte number. However, the mean fluorescence associated with ICAM-1 on monocytes and CD11a and CD18 expression on lymphocytes was related to clinical stage of disease. J. Leukoc. Biol. 56: 304–309; 1994.
Role of endogenous interferon-β in the restriction of HIV replication in human monocyte/macrophages
Authors: Gessani Sandra , Puddu Patrizia , Varano Barbara , Borghi Paola , Conti Lucia , Fantuzzi Laura , Gherardi Giovanni , Belardelli Filippo 
Published: January 2018

Abstract
In vitro culture of human monocytes results in a time-dependent differentiation into macrophages. Monocyte/macrophages were infected with HIV-1 Ba-L at different times after isolation and subsequent culture. When 7-day macrophages were infected in the presence of antibodies to interferon-β (IFN-β), a significant increase in HIV-1 p24 release was observed. This effect was not detected in 1-day monocytes. Treatment of 7-day cultured macrophages with HIV-1 rgp120 resulted in resistance to vesicular stomatitis virus infection. This rgp120-induced antiviral state was neutralized in the presence of antibodies to IFN-β. The overall results indicate that the infection of monocyte/macrophages with HIV-1 results in the induction of IFN-β, which, in turn, inhibits HIV-1 expression in macrophages. The finding that HIV-1 itself (possibly through its gp120) can induce a potent antiviral factor (IFN-β) in macrophages underlines the complex physiological function of these cells in maintaining normal homeostasis in vivo in response to virus infection. J. Leukoc. Biol. 56: 358–361; 1994.
In vitro activity of inhibitors of late stages of the replication of HIV in chronically infected macrophages
Authors: Perno Carlo-Federico , Aquaro Stefano , Rosenwirth Brigitte , Balestra Emanuela , Peichl Peter , Billich Andreas , Villani Nicoletta , Calio Raffaele 
Published: January 2018

Abstract
Because of the importance of macrophages in the pathogenesis of the disease caused by HIV, we investigated the efficacy of various anti-HIV drugs in human primary macrophages acutely or chronically infected by this virus. The results obtained for acutely infected macrophages show that dideoxynucleosides (AZT, ddI, and ddC), interferon-α and -γ, mismatched double-stranded RNA, Tat inhibitor, phosphorothioate antisense, and inhibitors of HIV protease, all significantly inhibit virus replication at concentrations far below those toxic for the cells. However, in macrophages in which proviral DNA is already integrated (chronically infected macrophages), only the three inhibitors of HIV protease induced significant virus inhibition at concentrations 100 or more times higher than those effective in acutely infected macrophages. Treatment of macrophages with macrophage colony-stimulating factor does not affect the anti-HIV efficacy of protease inhibitors. These results suggest that therapeutic strategies with activity for macrophages, including inhibitors of HIV protease, are worth pursuing in patients with HIV infection. J. Leukoc. Biol. 56: 381–386; 1994.
Presentation of endogenous tumor antigens to CD4+ T lymphocytes by murine melanoma cells transfected with major histocompatibility complex class II genes
Authors: Chen Peter W , Ullrich Stephen E , Ananthaswamy Honnavara N 
Published: January 2018

Abstract
In a previous study, we demonstrated that K1735 transfectants expressing either Kk or Ak antigens alone produced tumors in syngeneic mice, whereas transfectants that expressed both antigens were rejected. In this study, we investigated whether K1735 transfectants expressing Ak molecules can present endogenous tumor antigens to CD4+ T lymphocytes in the absence of normal accessory cells. Our results indicate that K1735 transfectants expressing Kk and Ak molecules presented antigen to both CD4+ and CD8+ T lymphocytes, whereas K1735 transfectants expressing only the Ak or the Kk antigen preferentially stimulated either CD4+ or CD8+ T cells. Analogous to endogenous antigens, K1735 transfectants expressing Ak molecules also presented exogenous hen egg lysozyme (HEL) to HEL-specific 3A9 hybridomas in the absence of normal accessory cells. These results demonstrate that K1735 murine melanoma cells expressing Ak molecules can function as antigen-presenting cells and that the generation of an effective antitumor immune response by K1735 melanoma cells expressing Kk and Ak antigens is due to their ability to present endogenous tumor antigens to both helper and cytotoxic T cells. J. Leukoc. Biol. 56: 469–474; 1994.