bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro invasiveness of CTL clones and in vivo dissemination of CTL hybridomas
Authors: La Rivière Geertie , Gebbinck Jacqueline WTM Klein , Schipper Cor A , Mooi Wolter J , Roos Ed 
Published: January 2018

Abstract
Activated spleen T cells are invasive in hepatocyte and fibroblast cultures, and this property is dominantly expressed in T cell hybridomas. The invasive potential of the hybrids correlates with their capacity to disseminate in vivo. We have used this model to study the invasive and migratory properties of cytotoxic T lymphocytes (CTLs). TWo murine CTL clones were highly invasive, independent of their state of activation. CTL hybridomas, derived from one of the clones, were similarly invasive. In vivo, CTL hybridoma cells disseminated to extravascular sites in the liver, kidneys, lungs, ovaria, tubae, uterus, and lymphoid, mesenchymal, and fat tissues. Within 7 to 14 days, 106 cells were lethal in 100% of mice. The adhesion molecules CD2, CD8, CD54, L-selectin, and CD49d (VLA-4 and LPAM-1 α-chain) were not expressed by all CTL hybridomas and therefore not indispensable for invasion in vitro and dissemination in vivo. In contrast, LFA-1 (CDlla/CD18), CD44, and VLA-6 (CD49f/CD29) were expressed on all hybrids. LFA-1 antibodies inhibited CTL hybridoma invasion in vitro, but antibodies inhibiting CD44-hyaluronate and VLA-6-laminin interaction had no effect. These results suggest that migration of cytotoxic T cells into non- inflamed tissues is independent of their activation state and does not require L-selectin, LPAM-1, CD2, and VLA-4. J. Leukoc. Biol. 53: 381–389; 1993.
Mechanisms of Kupffer cell cytotoxicity in vitro against the syngeneic murine colon adenocarcinoma line MCA26
Authors: Curley Steven A , Roh Mark S , Feig Barry , Oyedeji Caroline , Kleinerman Eugenie S , Kiostergaard Jim 
Published: January 2018

Abstract
We have previously demonstrated that in vivo activation or inhibition of Kupffer cell (KG) cytotoxic function can reduce or enhance, respectively, the hepatic tumor burden in a syngeneic murine colon adenocarcinoma (MCA26) tumor model. In the current study, we have performed in vitro experiments to define the possible mechanisms of KG cytotoxicity against MGA26 cells. Addition of either anti-tumor necrosis factor (TNF) or anti-interleukin-1α (IL-lα) antisera reduced KG cytotoxicity in coculture against MCA26 targets in a dose- dependent fashion; addition of these sera together resulted in approximately additive inhibition, suggesting the existence of parallel pathways for these effector molecules. Nitric oxide as a mediator of cytotoxicity by KCs in coculture with MCA26 cells was evaluated by two approaches. Activated KGs produced detectable levels of nitric oxide; however, activated KC exerted cytotoxicity against MCA26 targets in the absence of exogenous free L-arginine. Thus, TNF and IL-1 play major roles in producing murine KG cytotoxicity against MCA26 colon cancer cells in vitro, whereas reactive nitric oxides do not. J. Leukoc. Biol. 53: 715–721; 1993.
Suppression of human IgE antibody forming cell responses by IL-6
Authors: Kleiner Gary I , Auci Dominick L , Shaikh Altaf , Chice Soto M , Durkin Helen G 
Published: January 2018

Abstract
To study the effects of cytokines on human IgE antibody forming cells (AFCs), log phase U266 myeloma cells (3 × 103/ml), which secrete immunoglobulin E (IgE), were cultured for 0-24 h with and without cytokine or with or without antibodies against various cytokines. The numbers of IgE AFCs were determined in ELISPOT assay. We found that interleukin-6 (IL-6) suppressed (to 95%) whereas anti-IL-6 increased (to 148%) the numbers of IgE AFCs and that both worked in a dose- dependent fashion. IL-4 and interferon-γ (IFN-γ) also suppressed IgE AFC responses in a dose-dependent fashion. However, antibodies to these cytokines had no effect. In contrast, IFN-α increased (to fourfold) the numbers of IgE AFCs in a dose-dependent fashion. The data are the first to show a suppressive effect of IL-6 on human IgE responses and may also suggest a role for IL-6 in the treatment of atopic disease.
Particle-induced in vivo priming of alveolar macrophages for enhanced oxidative responses: a novel system of cellular immune augmentation
Authors: Myrvik Quentin N , Gristina Anthony G , Giridhar Girish , Hayakawa Hiroshi 
Published: January 2018

Abstract
A novel system for priming adult rabbit alveolar macrophages (AMs) in vivo for markedly enhanced oxidative responses is described. When adult rabbits were injected intravenously (i.v.) with 1- to 5-μm particles such as zymosan, latex particles, or heat-killed bacille Calmette-Guérin, AMs were primed in 1-3 days for greatly enhanced phorbol myristate acetate (PMA)- or opsonized zymosan (Op-zym)-elicited chemiluminescent (CL) responses. Intratracheal (i.t.) injection of zymosan particles also primed AMs for enhanced PMA- or Op- zym-elicited CL responses. AMs obtained from particle- injected rabbits showed up to 100-fold higher levels of PMA-elicited CL responses than AMs from normal rabbits. In contrast, Op-zym failed to prime normal AMs in vitro for enhanced CL responses. Whereas AMs could not be primed in vivo with an i.v. injection of particles of - 24 μm diameter, AMs could be primed if the particles were administered by the i.t. route. The priming appears to be independent of particle types. The priming effect was of short duration and declined after 5 to 7 days. The possibility that this system represents the primitive cellular immune response found in invertebrates is discussed. The potential use of this system as a means of immune augmentation prompts further investigation.
Enhanced hepatic clearance of intravenously administered sterically stabilized microspheres in zymosan-stimulated rats
Authors: Moghimi S M , Hedeman H , Christy N M , Ilium L , Davis S S 
Published: January 2018

Abstract
The blood clearance and organ deposition of sterically stabilized (poloxamine-908 coated) polystyrene microspheres of two different sizes (60 and 220 nm in diameter) were compared in control and zymosan- stimulated rats 3 h after intravenous administration. Poloxamine coating dramatically decreased the uptake of 60-nm microsphcres by organs of the reticuloendothelial system and, concomitantly, kept microspheres in the blood. Large poloxamine-coated microspheres (220 nm) initially remained in the blood, but eventually a large fraction of these microspheres was filtered by the spleen. Daily administration of zymosan produced a marked increase in the intravascular clearance of the large, but not the small, poloxamine-coated microspheres. The enhanced intravascular clearance of large poloxamine- coated microspheres in zymosan-treated rats was the result of hepatic sequestration. On the other hand, the splenic filtration of these microspheres was depressed by 225% below the control values, despite the dramatic increase in spleen size of zymosan-treated rats. Preincubation of large poloxamine-coated microspheres in serum derived from both the control and zymosan-treated animals suggested that the enhanced hepatic uptake of large sterically stabilized microspheres following zymosan stimulation was not the result of “specific opsonization” processes. Instead, the changes in the proliferative as well as the phagocytic response of Kupffer cells appeared to be responsible for these observations. The preferred hepatic uptake of large poloxamine-coated microspheres, as opposed to smaller particles, is suggested to be due to differences in surface characteristics and the properties of microspheres. These may include differences in polymer density and the surface conformation of the polyoxyethylene segments of the polymer in the biological environment and the way they interact with both plasma components and the macrophage surface. These observations could be of importance in the use of sterically stabilized drug carriers for delivery of therapeutic agents to sites other than the reticuloendothelial system in clinical conditions associated with globally or regionally enhanced reticuloendothelial activity.
Involvement of inflammatory mediators in macrophage antitumor activity
Authors: Bonta Ivan L , Ben-Efraim Shlomo 
Published: January 2018

Abstract
This review describes the potential role of macrophages in defense against cancer cells and the regulatory involvement of inflammatory mediators in this role. Interactions between macrophage-derived cytokines (tumor necrosis factor a, interleukin-1, IL-6) and their interrelationships with eicosanoids (mainly the cyclooxygenase product prostaglandin E2 and some lipoxygenase metabolites) represent a network that controls the expression of antitumor activity of macrophages either in a cell-to-cell contact system between the effector and the target tumor cell or as cell-free soluble products. Attention is given to the influence of tumor burden on production of cytokines and eicosanoids by macrophages and to the production of these mediators by tumor cells. Emphasis is placed on the roles of TNF-α and PGE2 in links between inflammatory and antitumor functions of macrophages. Finally, the perspectives and still existing problems in clinical implications of macrophage-derived cytokines are discussed in terms of a conceivable macrophage-directed immunotherapy of cancer.
The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection
Authors: Huffnagle Gary B , Lipscomb Mary F , Lovchik Julie A , Hoag Kathleen A , Street Nancy E 
Published: January 2018

Abstract
Moderately virulent strains of Cryptococcusneoformans, inoculated via the trachea, cause a pulmonary infection in BALB/c mice that was gradually resolved by T lymphocyte-dependent mechanisms. The current studies, using monoclonal antibodies to deplete T cell subsets, demonstrated that CD4+ and CD8+ T cells combined to mediate a prominent pulmonary inflammatory infiltrate that included lymphocytes, macrophages, neutrophils, and eosinophils. The inflammatory response peaked 2 weeks after infection and coincided with the beginning of gradual pulmonary clearance of the infection. CD4/CD8 double, deficiency (4-8-) markedly reduced the influx of all cells into the lungs. A CD4 deficiency had a more profound effect on the total number of inflammatory cells recruited to the lungs than a CD8 deficiency. Depletion of either CD8+ or CD4+ T cells significantly decreased pulmonary macrophages and neutrophils, but only a CD4 deficiency prevented the influx of eosinophils. Recruitment of CD8+ T cells occurred independently of CD4+ T cells, but CD4+ T cell recruitment to the lungs was significantly reduced in CD8-deficient mice. Mitogen-stimulated infiltrating lung lymphocytes from infected 4+8+ mice secreted both T helper cell type 1 (Th1) [interferon-γ (IFN-γ) and interleukin-2 (IL-2)] and Th2 (IL-4, IL-5, and IL-10) cytokines. CD4 deficiency resulted in loss of T cells secreting IL-4, IL-5, and IL-10. However, residual CD8+ T cells still secreted IL-2 and IFN-γ. Lung T cells from CD8-deficient mice secreted similar levels of IL-4, IL-5, and IL-10 on a per lung basis compared with 4+8+ mice despite decreased numbers of CD4+ T cells, but secreted reduced levels of IFN-γ. These experiments indicate that (1) CD4+ T cells play a dominant role in recruiting macrophages and granulocytes to the lung and (2) CD8+ T cells also mediate cellular recruitment, increase the magnitude of CD4+ T cell numbers in the infiltrate, and contribute to the local secretion of IFN-γ. Thus, these studies demonstrate that CD8+ T cells can independently mediate an inflammatory response to a large, particulate, extracellular antigen, a role heretofore attributed almost solely to CD4+ T cells. J. Leukoc. Biol. 55: 35–42; 1994.
Interleukin-2 suppresses activated macrophage intracellular killing activity by inducing macrophages to secrete TGF-β
Authors: Nelson Barbara J , Danielpour David , Rossio Jeffrey L , Turpin Jim , Nacy Carol A 
Published: January 2018

Abstract
Phorbol myristate acetate (PMA) treatment of an EL-4 thymoma cell line (EL-4farrar) induced secretion of a factor that inhibited intracellular killing of Leishmania major amastigotes by activated macrophages. Analysis of the cytokines produced by EL-4 cells after PMA stimulation identified interleukin-2 (IL-2, 2500 U/ml), IL-4 (1280 U/ml), interferon-γ (IFN-γ; 100 U/ml), and granulocyte-macrophage colony-stimulating factor (GM-CSF; 50 U/ml). Neither tumor necrosis factor nor transforming growth factor β (TGF-β) was detected. Each of the cytokines present in EL-4 fluids was assessed for capacity to activate macrophages for destruction of parasites or to suppress intracellular killing. IFN-γ and GM-CSF both activated macrophages to kill Leishmania; I L-2 and IL-4 had no activity for induction of this anti-microbial effector function. IL-2 and IL-4 were tested for their capacity to inhibit lymphokine- or IFN-γ-induced destruction of L. major by macrophages: IL-4 was ineffective, but IL-2 markedly suppressed the activation of macrophages for intracellular killing. Addition of ≥ 10 U/ml of IL-2 at the time of infection, or up to 4 h before, blocked up to 100% of the capacity of activated macrophages to kill intracellular amastigotes. Immunoaffinity treatment of EL-4 fluids with anti-IL-2 antibody resulted in &gt;80% reduction in suppression of intracellular killing. The suppressive effects of IL-2 were not direct, but mediated by TGF-β. IL-2 induced resident peritoneal macrophages to secrete &gt;5000 pg/ml TGF-β1, a quantity that is &gt; 500-fold higher than constitutive background levels (20–40 pg/ml) and is sufficient to block intracellular killing activities. This increase in secretion of TGF-β was not dependent increases in TGF-β1 mRNA. Treatment of cultures with EL-4 fluids or recombinant IL-2 in the presence of antibody to TGF-β1 blocked the suppressive activity of both. Thus, IL-2 was the major suppressor factor in EL-4 fluids, and it acted indirectly through the induction and autocrine action of TGF-β. J. Leukoc. Biol. 55: 81–90; 1994.
A single assay for measuring the rates of phagocytosis and bacterial killing by neutrophils
Authors: Hampton Mark B , Vissers Margret C M , Winterbourn Christine C 
Published: January 2018

Abstract
We have developed a method that enables the rates of phagocytosis and killing of bacteria by neutrophils to be measured in a single assay. Neutrophils were incubated with bacteria, and at specific intervals were separated from uningested bacteria by low speed centrifugation. Rates of phagocytosis and killing were calculated from the decrease in number of extracellular bacteria and change in the number of intracellular bacteria. Both phagocytosis and killing were shown to follow first-order kinetics, and rate constants were calculated without having to separate the assay into two phases. In contrast to two-step methods, our method measures killing from the moment the neutrophils start ingesting the bacteria, and also eliminates the need to halt neutrophil activity temporarily and restart the assay after the extracellular bacteria have been removed. We obtained reproducible results for the phagocytosis and killing of Staphylococcus aureus (t1/2 = 9 min and 6 min respectively) and Escherichia coli (t1/2 = 10 min and 2 min respectively). We also were able to detect a 56% impairment in the rate of killing of S. aureus by neutrophils from an individual with a low level of myeloperoxidase. J. Lcukoc. Biol. 55: 147–152; 1994.
Influence of interleukin-2 infusion on cell cycle kinetics in the Walker-256 carcinosarcoma
Authors: Wan Jennifer M -F , Bistrian Bruce R , Figoni Mary-Ann T , Istfan Nawfal W 
Published: January 2018

Abstract
The effect of recombinant human interleukin-2 (IL-2) on tumor cell cycle kinetics was evaluated in rats bearing the Walker-256 carcinosarcoma. Seven days after implantation, tumor-bearing rats were infused intravenously with IL-2 at a dose of 500 mg/kg body weight or 5% dextrose for 6 h. Tumor cell mean DNA synthesis time (Tdna), labeling index, potential doubling time (Tpot)) and growth fraction (GF) were determined in vivo by use of bromodeoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis using flow cytometry. IL-2 treatment significantly reduced the relative number of S-phase cells by 11.9% and increased the number of cells in the G0/G1 phase by 9.4%. The labeling index was reduced from 41.3 ± 2.5% to 32.7 ± 1.2% (P &lt;. 01). Estimates of TDNA derived from the change in BrdUrd movement relative to DNA content were not affected by IL-2 treatment. Based on these cytokinetic changes, IL-2 infusion significantly increased tumor Tpot from 15.3 ± 0.3 h to 21.5 ± 0.2 h (P &lt; .001) and reduced GF from 1.01 ± 0.07 to 0.83 ± 0.01 (P &lt; 0.001). The inhibitory effect of IL-2 infusion on tumor cell growth, which may be either direct or secondarily mediated by other factors, contrasts with other stimulatory effects of this cytokine on lymphoid cell proliferation. J. Leukoc. Biol. 55: 241–247; 1994.
Quantitative discrimination of hepatic reticuloendothelial clearance and phagocytic killing
Authors: Klein Andrew , Zhadkewich Michael , Margolick Joseph , Winkelstein Jerry , Bulkley Gregory 
Published: January 2018

Abstract
An in vivo assay to quantify simultaneously two important components of hepatic reticuloendothelial system (RES) function—clearance and phagocytic killing—was developed in the rat. Intravenously injected E. coli labeled with Na51Cr and 5-[123I]-iodo-2′-deoxyuridine were cleared rapidly from the blood primarily by the liver. While hepatic 51Cr levels remained stable for 24 h following inoculation and provided a reliable measurement of clearance, hepatic 125I decreased over time. Hepatic 125I, calculated by sampling whole liver homogenates, accurately reflects the number of viable bacteria recovered from quantitative cultures of the same homogenates, thus validating this assay as a measure of bacteria killing. Pre-treatment of rats with substances previously shown to affect RES function (gadolinium, zymosan, and sheep erythrocytes) were found to selectively modulate clearance and/or killing. The correlation between hepatic isotope levels and viable hepatic bacteria, the gold standard for assessing the capacity of the liver to remove organisms from the blood and kill them, was preserved under conditions of up- and down-regulation of RES function. The ability to quantitatively discriminate two distinct components of the hepatic RES should provide a useful tool for future investigations of altered RES function. J. Leukoc. Biol. 55: 248–252; 1994.
β
2-Adrenoceptor agonists regulate the IL-4-induced phenotypical changes and IgE-dependent functions in normal human monocytes
Authors: Paul-Eugène Nathalie , Kolb Jean Pierre , Damais Chantal , Abadie Annie , Mencia-Huerta Jean Michel , Braquet Pierre , Bousquet Jean , Dugas Bernard 
Published: January 2018

Abstract
The β 2-adrenoceptor agonists salbutamol and fenoterol were tested for their regulatory effects on human monocyte phenotype and functions, either alone or in combination with interleukin-4 (IL-4). These drugs enhanced in a dose-dependent manner the IL-4-induced membrane and mRNA expression of the low-affinity receptor for immunoglobulin E (IgE) (CD23), as well as the release of its soluble form, sCD23. Salbutamol and fenoterol alone elicited expression of the monomorphic β 2-chain (CD18) of the leukocyte functional antigen (LEA1) family. This effect appeared to be restricted to CD11b (CR3) and CD11c (gp 150–95), because CD11a (LFA-1α chain) was not modified, β 2-Adrenoceptor stimulation was also found to potentiate the effect of IL-4 on CD11b, CD11c, and CD18 expression. In contrast, these agents alone did not alter the level of major histocompatibility complex class II and CD14 antigens or modify their respective up- and down-regulation by IL-4. Ligation of CD23 on IL-4-preincubated (CD23*) monocytes with IgE/anti-IgE immune complexes induced the release of free radicals nitric oxide and of the proinflammatory mediators IL-6 and thromboxane B2 (TxB2). Addition of salbutamol, inactive alone, potentiated the generation of superoxide anion and of nitric oxide generation, as well as the production of IL-6 and TxB2 triggered by CD23 ligation. These results indicate that β 2-adrenoceptor stimulation potentiates in vitro the IL-4-induced phenotypical and functional changes on monocytes and suggest that such an interaction could occur in IgE-dependent immune reactions. J. Leukoc. Biol. 55: 313–320; 1994.
Differential RNA regulation by staphylococcal enterotoxins A and B in murine macrophages
Authors: Chapes Stephen K , Beharka Alison A , Hart Mark E , Smeltzer Mark S , Landolo J J 
Published: January 2018

Abstract
Staphylococcal enterotoxin A (SEA) is significantly better than enterotoxin B (SEB) in activating tumor necrosis factor (TNF) secretion by B6MP102 cells. Both toxins bound to B6MP102 cells; however, SEB competed less effectively with SEA than SEA competed with SEB. This suggested that receptors unique to SEA were present on B6MP102 cells. Signal transduction occurred in response to both toxins. Within 30 s after addition, SEA and SEB significantly increased the F-actin concentration in B6MP102 cells. However, only SEA induced increased TNF mRNA levels. B6MP102 cells incubated with interferon-γ and SEB secreted TNF. However, enhanced mRNA expression was delayed and the concentration of TNF secreted was less than that of B6MP102 cells stimulated with SEA. Although these data suggest that receptors unique to SEA are present on B6MP102 cells, they also indicate that staphylococcal enterotoxins differentially regulate TNF at the RNA level, perhaps because of differences in binding to the plasma membrane. J. Leukoc. Biol. 55: 523–529; 1994.
Expression and visualization during cell cycle progression of alkaline phosphatase in B lymphocytes from C3H/HeJ mice
Authors: Souvannavong Vongthip , Brown Spencer , Sarih M’hammed , Adam Arlette 
Published: January 2018

Abstract
The expression of alkaline phosphatase (APase) activity by purified B cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice was determined. Optimal APase activity was expressed after costimulation with interleukin-5 and dextran sulfate (DXS), whereas LPS, which is highly effective on B lymphocytes from normal mice, was unable to induce enzyme expression, even in the presence of DXS. The simultaneous determination by flow cytometry of both cellular APase, by using a fluorescent azo dye technique, and DNA content showed that APase was highly expressed by about one-tenth of cells in G1 phase, whereas it was present in more than 50% of cells in S and G2/M phases. The enzyme, as visualized by confocal microscopy after cell sorting on the basis of DNA content, was found to be, localized mainly in vesicular structures distributed throughout the cytoplasm in G1 cells. It was distributed in patches and essentially localized at the cell periphery in S cells, whereas clear capping of activity was observed in G2/M cells. J. Leukoc. Biol. 55: 626–632; 1994.
Generation of an ovine bone marrow-derived myelomonocyte-like cell line by retroviral-mediated transformation. Immunological characterization and the effect of cytokines and lipopolysaccharides
Authors: John Huw A , Deane David , Haig David 
Published: January 2018

Abstract
A cell line (designated BMpXTl) was generated from sheep bone marrow using the Moloney murine leukemia virus-based retroviral vector pXTl. BMpXTl cells resembled mature alveolar macrophages in being adherent and esterase positive, in expressing certain cell surface antigens, and in secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) when stimulated by ovine interferon-γ and lipopolysaccharide (LPS) in combination. The absence of a proliferative response to ovine GM-CSF and macrophage colony-stimulating factor, the absence of other cell antigens found in mature macrophages, and lsw-efficiency phagocytosis suggested that the cells may be at an intermediate to late stage of myelomonocytic differentiation. J. Leukoc. Biol. 55: 785–792; 1994.