bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential inhibitory effects of interleukin-10, interleukin-4, and dexamethasone on staphylococcal enterotoxin-induced cytokine production and T cell activation
Authors: Krakauer Teresa 
Published: January 2018

Abstract
The cytokine profile of human peripheral blood mononuclear cells (PBMC) stimulated by staphylococcal enterotoxin (SE) A and B was examined. Production of tumor necrosis factor (TNFα), interleukin (IL)-1, IL-6, IL-2, and gamma interferon (IFN-γ) was observed. In contrast, Th2 cytokines IL-4 and IL-10 were absent from SEA- or SEB-stimulated PBMC. Moreover, adding IL-10 to SE-stimulated PBMC inhibited the production of IL-1, IL-6, TNFα, and IFNγ by 50 to 80% but had less effect (8–30%) on T cell proliferation. IL-4 was less effective than IL-10 in inhibiting cytokine production and enhanced T cell proliferation by SEA or SEB. The antiinflammatory agent, dexamethasone, was the most potent agent in controlling the SE-mediated effects as evidenced by inhibited T cell proliferation (55%) and reduced levels of IL-1, IL-6, and IFNγ (60% to 100%) and TNFα (50%). Reducing levels of toxic mediators such as TNFα, IL-1, IL-6, and IFNγ by dexamethasone in SE-induced T cell responses may be a useful therapeutic strategy to circumvent SE toxicity and pathogenesis. J. Leukoc. Biol. 57: 450–454; 1995.
Selective sensitivity of macrophages to cytotoxicity by inhibitors of macromolecular synthesis: induction of apoptosis
Authors: Lewis J G , Adams D O , Fan S 
Published: January 2018

Abstract
Initial studies designed to measure the effect of inhibiting RNA synthesis by dactinomycin on macro phage functions revealed that the cells were uniformly killed at concentrations that have been routinely used to inhibit RNA synthesis in other cell types. We, thus, deter mined the dose curve for the cytotoxicity of dactinomycin for macrophages and two other cell types, L929 cells and splenic lymphocytes Macrophages were extremely sensitive to the cytotoxicity of dactinomycin compared to the other cell types. Submicromolar concentrations that in duced 100% cytotoxicity in macrophages caused little death in L929 cells or lymphocytes. Concentrations of dactinomycin that inhibited RNA synthesis by 40% in macrophages induced almost complete cell death but in hibition of over 80% of RNA synthesis in L929 cells or lymphocytes induccd no measurable cytotoxicity. Macro phages did take up more dactinomycin than other cells but the amount was not sufficient to account for the large differences in cytotoxicity. We next tested the effects of doxorubicin and cyclohcximide and found that macro phages were also extremely sensitive to killing by these compounds, and there was a very close association be tween the amount of inhibition of protein synthesis and the amount of toxicity. The morphology of macrophages exposed to these agents was consistent with death by apoptosis. This was further supported by assays measuring membrane integrity and DNA fragmentation. These data demonstrate that inhibition of macromolecular syn thesis in macrophages, by different mechanisms, causes macrophages to undergo apoptosis. They further suggest that, in contrast to other cell types that require protein synthesis for apoptosis, macrophages require the synthe sis of certain proteins to avoid apoptosis. J. Leukoc. Biol. 57: 635–642; 1995.
Interaction of GM-CSF and IL-3 with the common β-chain of their receptors
Authors: Bagley Christopher J , Woodcock Joanna M , Hercus Timothy R , Shannon M Frances , Lopez Angel F 
Published: January 2018

Abstract
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL-3) are cytokines active in both normal and abnormal hemopoiesis, inflammation, and immunity. Their biological activity is mediated via receptors that comprise a ligand-specific α chain and a β chain that is common to the GM-CSF, IL-3, and IL-5 receptors. To understand the mechanism of action of GM-CSF and IL-3 in both normal and pathological conditions, we are seeking to define the structural elements required for ligand/receptor and receptor/receptor contact and their role in cellular activation. To this end we have identified a conserved motif in the first helix of GM-CSF, Glu21 that is critical for high affinity binding and biological activity. Charge-reversal mutagenesis of this residue generates a GM-CSF analogue that is devoid of biological activity and can antagonize the activity of wild-type GM-CSF. This probably results from the selective deficiency in interaction with the β chain of the receptor and suggests that similar antagonists for IL-3 and IL-5 are also feasible. Complementary mutagenesis studies on the receptor β chain have identified the putative B’-C’ loop in the membrane-proximal domain as being critical for the high affinity binding of GM-CSF but not IL-3. Characterization of the specificity of sites of interaction between the ligands and receptors may permit the design of specific or generic antagonists that may have important therapeutic implications. J. Leukoc. Biol. 57: 739–746; 1995.
Endotoxin infusion in anesthetized sheep is associated with intrapulmonary sequestration of leukocytes that immunohistochemically express tumor necrosis factor-α
Authors: Cirelli Rosemary A , Carey Lisa A , Fisher Jill K , Rosolia David L , Elsasser Ted H , Capema Thomas J , Gee Marlys H , Albertine Kurt H 
Published: January 2018

Abstract
Plasma levels of tumor necrosis factor-α (TNF-α) peak between 2 and 4 h during a 12-h continuous infusion of endotoxin in awake sheep. We hypothesized that a source of this TNF-α is the pool of leukocytes that accumulate in the pulmonary circulation. To test this hypothesis, we physiologically monitored six anesthetized sheep during baseline and 4-h endotoxin infusion periods (10 ng/kg min). We obtained open-lung biopsies at baseline and at 20 min and 2 and 4 h during the endotoxin infusion period for immunohistochemical localization of TNF-α. The plasma concentration of TNF-α increased from an average baseline concentration of 0.06 ± 0.03 ng/ml (mean ± SD) to a peak of 1.40 ± 0.28 ng/ml at 2 h of the endotoxin infusion. We observed increased cytoplasmic TNF-α immunoreactivity in situ among neutrophils and intravascular mononuclear phagocytes during the endotoxin infusion compared with baseline. Also, the number of immunopositive leukocytes increased in the pulmonary circulation during the continuous infusion of endotoxin. We conclude that TNF-α-producing leukocytes accumulate in the pulmonary circulation during endotoxemia. These cells probably contribute to both the rise in the circulating levels of TNF-α and the development of acute lung injury. J. Leukoc. Biol. 57: 820–826; 1995.
Elevation of rainbow trout Oncorhynchus mykiss macrophage respiratory burst activity with macrophage-derived supernatants
Authors: Jang Seon I , Hardie Laura J , Secombes Christopher J 
Published: January 2018

Abstract
A variety of supernatants were prepared by stimulating rainbow trout Oncorhynchus mykiss head kidney macrophages with lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), or a leucocyte-derived macrophage-activating factor (I-MAF), individually and in combination. If generated using a 12-h stimulation period, such supernatants were found to elevate significantly the respiratory burst activity of target macrophages; that is, they contained a macrophage-derived MAF (m-MAF), but supernatants generated using a shorter incubation period showed no significant activity. Combinations of these treatments were particularly effective in generating m-MAF–containing supernatants. The elevation of respiratory burst activity by supernatants generated using combined treatments could be partially inhibited by prior treatment of the target macrophages with anti-TNF-α receptor 1 (TNFR1) monoclonal antibodies (mAbs). Similarly, treatment of macrophages with combinations of 1-MAF and m-MAF generated supernatants with potent m-MAF activity and this activity was partially inhibited by prior treatment of the target cells with anti-TNFR1 mAb. In addition, the presence of anti-transforming growth factor β1 (TGF-β1) serum while generating these latter supernatants resulted in significantly increased m-MAF activity. Such data suggest that fish leukocytes secrete a variety of potent macrophage-activating (TNF-α) and -deactivating (TGF-β) factors. J. Leukoc. Biol. 57: 943–947; 1995.
Proteases and protease receptors in modulation of leukocyte effector functions
Authors: Altieri Dario C 
Published: January 2018

Abstract
Cellular immune responses depend on regulated pathways of intracellular signal transduction and leukocyte activation. Although these mechanisms are coordinated by a variety of leukocyte-restricted effector molecules, recent observations have uncovered a novel role of proteases in transducing outside-in signals of leukocyte activation. Through regulated, receptor-mediated recognitions, coagulation and fibrinolytic enzymes or effector cell granular proteases influence monocyte motility and chemotaxis, modulate pleiotropic cytokine responses, contribute to mononuclear cell proliferation, or induce target cell apoptosis. Overall, these mechanisms define a novel interface between general inflammatory reactions, invariably characterized by activation of blood protease cascades, and specialized aspects of cellular immune functions. J. Leukoc. Biol. 58: 120–127; 1995.
Phorbol ester-induced priming of superoxide generation by phosphatidic acid-stimulated neutrophils and granule-free neutrophil cytoplasts
Authors: Siddiqui Rafat A , English Denis , Harvey Kevin , Cui Yi , Martin Margaret I , Wentland John , Akard Luke , Jansen Jan , Thompson James , Garcia Joe G N 
Published: January 2018

Abstract
This study was undertaken to examine the mechanisms involved in polymorphonuclear leukocyte superoxide release stimulated by exogenous phosphatidic acid (PA). Unlike the immediate burst of superoxide release affected by membrane-permeable dioctanoyl-glycerol (DiC8-DAG), dioctanoyl phosphatidic acid (DiC8-PA) induced superoxide release after a lag period of 5–20 min. This period was considerably reduced or eliminated when cells were primed by substimulatory levels of phorbol myristate acetate (PMA). Granule-depleted neutrophil cytoplasts also responded to DiC8-PA with a burst of superoxide generation. Activation of the cytoplast superoxide generating system in response to DiC8-PA was also significantly faster after cells had been preexposed to substimulatory levels of PMA, indicating that at least a portion of the priming mechanism was independent of PMA-induced degranulation. To further examine the potential mechanism of PMA priming of responses to PA, we evaluated the activity of neutrophil ecto-phosphatidic acid phosphohydrolase (ecto-PA phosphohydrolase), which generates diacylglycerol from exogenous PA. PMA priming had no discernable effect on the activity of this enzyme. In addition, propranolol, an inhibitor of PA phosphohydrolase, did not selectively inhibit PMA priming of neutrophil responses to DiC8-PA, indicating that priming did not result from acceleration of DiC8-PA hydrolysis. We therefore investigated the possibility that activation of protein kinase C was the basis of the primed response. Several semiselective protein kinase C inhibitors (calphostin C, H-7, and acylmethylglycerol) inhibited DiC8-DAG- and DiC8-PA-induced superoxide release as well as PMA-primed responses to approximately the same extent. These results are consistent with the hypothesis that neutrophil responses to phosphatidate are mediated by diglyceride generated by the action of ecto-PA phosphohydrolase. PMA priming does not result from increased catalytic activity of ecto-PA phosphohydrolase but rather seems to result from potentiation of an intermediate involved in the cells’ response to multiple stimuli. J. Leukoc. Biol. 58: 189–195; 1995.
Discrete pathways for arachidonic acid release from tannin versus β-glucan-stimulated rabbit alveolar macrophages
Authors: Kennedy Michael T , Bates Philip J , Wheatley Christine L , Rohrbach Michael S 
Published: January 2018

Abstract
Previously, we observed both tannin and β-glucan to be agonists for arachidonic acid (AA) release from rabbit alveolar macrophages. Although tannin inhibited reincorporation of exogenous AA, β-glucan had no apparent effect, suggesting separate signal transduction pathways leading to elevated AA levels. In this study alveolar macrophages were pretreated with the tyrosine phosphatase inhibitor sodium orthovanadate then stimulated with either condensed tannin or β-glucan. Vanadate exerted opposing effects on AA release. Furthermore, vanadate reversed the ability of tannin to inhibit reacylation. Additional studies using the phospholipase A probe bis-BODIPY-C11-i-PC indicated that although the known phospholipase A2 activators, calcium ionophore A23187, insoluble immune complexes, and β-glucan, generated an increase in fluorescence consistent with phospholipase A activation, tannin had no effect. These findings suggest the increase in free AA resulting from stimulation of macrophages by either tannin or β-glucan is produced via two different mechanisms. J. Leukoc. Biol. 58: 241–248; 1995.
Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1α,25-dihydroxyvitamin D3 and cytokines
Authors: Boltz-Nitulescu George , Wiilheim Martin , Spittler Andreas , Leutmezer Fritz , Tempter Clemens , Winkler Susanne 
Published: January 2018

Abstract
The effects of lα,25-dihydroxyvitamin D3/caldtriol on the expression of Fc receptors (FcR) for IgA (FcαR), IgE (FcRII), and IgG (FcγR) on human peripheral blood monocytes and the cell lines U937, THP-1, and Mono Mac-6, in combination with various cytoldnes, was examined by flow cytometry. On both monocyte-derived macrophages and the myelomonocytic cell lines, FcαR/CD89 expression was induced by caldtriol alone and additively in combination with tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor. Constitutive and mterleukin-4 (IL-4)-driven FcRD/CD23 expression was markedly diminished on caldtriol-treated U937 cells and monocytes. FcRII was also triggered by IFN-γ, TNF-α, and IL-6 on all the cell lines, an effect blocked by caldtriol. On monocytes, the basal level and IFN-γ-induced FcγRI/CD64 expression was down-regulated by caldtriol and IL-4. The expression of FcγRII/CD32 on monocytes was strongly suppressed by caldtriol. Transforming growth factor-β induced FcγRIII/CD16 on monocytes, an effect opposed by caldtriol. The ability of caldtriol-treated monocytes to phagocytose IgG-sensitized ox erythrocytes was diminished. Our results demonstrate that caldtriol, alone or in combination with cytokines, modulates FcαR, FcRII, FcγRI, and FcγRII expression on human mononudear phagocytes, as well as FcγR-mediated phagocytosis. J. Leukoc. Biol. 58: 256–262; 1995.
Ultrastructural immunogold localization of subcellular sites of TNF-α in colonic Crohn’s disease
Authors: Beil Waltraud J , Weiler Peter F , Peppercorn Mark A , Galli Stephen J , Dvorak Ann M 
Published: January 2018

Abstract
Tumor necrosis factor-α, a proinflammatory cytokine, might have an important role(s) in initiating, modifying, and/or sustaining chronic inflammatory processes such as those that characterize Crohn’s disease, an inflammatory bowel disease of unknown etiology. We used an immunogold ultrastructural morphometric approach to localize tumor necrosis factor-α in colonic Crohn’s disease biopsies. Tumor necrosis factor-α was present in seven cell types (fibroblasts, eosinophils, mast cells, macrophages, colonic epithelial absorptive cells, Paneth cells, neutrophils). Tumor necrosis factor-α-containing subcellular organelles included lipid bodies (fibroblasts, eosinophils, macrophages, mast cells, colonic epithelial cells, neutrophils), secretory granules (eosinophils, Paneth cells), phagolysosomes (macrophages, colonic epithelial cells), and Golgi structures and vesicle membranes (neutrophils). A gradient of extracellular tumor necrosis factor-α immunoreactivity surrounded eosinophils, mast cells, and macrophages. P values of gold counts/μm2 were significant for all cells, organelles, and extracellular spaces measured, and all positive structures significantly exceeded the background labeling density/μm2. Specificity controls (normal rabbit serum, tumor necrosis factor-α-absorbed primary antibody) either failed to label these sites or gave markedly reduced specific tumor necrosis factor-α labeling, respectively. These findings represent the first ultrastructural localization of the subcellular sites of TNF-α in vivo in seven cell lineages in human colonic tissues.
Cloning, expression, and functional characterization of rat MIP-2: a neutrophil chemoattractant and epithelial cell mitogen
Authors: Driscoll Kevin E , Hassenbein Diana G , Howard Brian W , Isfort Robert J , Cody David , Tindal Michael H , Suchanek Maureen , Carter Janet M 
Published: January 2018

Abstract
Macrophage inflammatory protein-2 (MIP-2) is a member of a family of cytokines that play roles in inflammatory, immune, and wound healing responses. To clone the cDNA for rat MIP-2, RNA was isolated from the lungs of Fischer 344 rats after instillation of lipopolysaccharide. Reverse transcription-polymerase chain reaction was performed by using synthetic oligonucleotide primers designed from the mouse MIP-2 cDNA sequence. A cDNA containing the coding region of rat MIP-2 was cloned and sequenced. Comparison to the mouse MIP-2 cDNA demonstrated 90.3% homology at the nucleotide level and 86% homology at the amino acid level. The rat MIP-2 cDNA was expressed in Escherichia coli and protein evaluated for bioactivity. The recombinant rat MIP-2 was chemotactic for rat neutrophils but did not stimulate migration of rat alveolar macrophages or human peripheral blood eosinophils or lymphocytes. In addition, the recombinant rat MIP-2 and the related rat chemokine, KC/CINC stimulated proliferation of rat alveolar epithelial cells but not fibroblasts in vitro.
Natural resistance to infection with intracellular parasites: molecular genetics identifies Nramp1 as the Bcg/Ity/Lsh locus
Authors: Vidal Silvia , Gros Philippe , Skamene Emil 
Published: January 2018

Abstract
Natural resistance to infection with intracellular parasites is controlled in the mouse by the expression of a locus or group of loci on chromosome 1 alternatively named Bcg, Lsh, and Ity. Bcg affects the capacity of mature tissue macrophages to restrict the intracellular proliferation of ingested parasites in the reticuloendothelial organs of the host during the early phase of infection. This review summarizes our molecular genetic approach to the isolation and characterization of the Bcg locus. We have used a positional cloning strategy based on genetic and physical mapping, YAC cloning, and exon trapping to isolate a candidate gene for Bcg, named Nramp1, which codes for a macrophage-specific polytopic protein with 12 predicted transmembrane domains and a consensus transport motif. Sequence analysis of Nramp1 cDNA clones from 27 Bcgr and Bcgr mouse strains reveals that susceptibility to infection (Bcgr) is associated with a single nonconservative Gly to Asp substitution at position 169 within predicted transmembrane domain 4 of the Nramp protein. Cloning experiments and homology search in available databases demonstrated that the Nramp1 gene belongs to a small gene family with several members in vertebrates and in such distantly related species as yeast and plants. Nramp proteins share a remarkable degree of similarity, with strong amino acid sequence conservation in the transmembrane domains, suggesting a common transport function for the Nramp family. Finally, we generated Nramp1−/- gene knockout mice, and analysis of their phenotypic characteristics established that (1) Nramp1 plays a key role in natural defense against infection with intracellular parasites and therefore demonstrated allelism between Nramp1 and Bcg/Ity/Lsh, (2) Nramp1 functions by a novel cytocidal/cytostatic mechanism distinct from those expressed by the activated macrophage, and (3) the Nramp1Asp169 allele of Bcgr inbred strains is a null allele, pointing to a critical role of this residue in Nramp1 function.
Role of the FcγR subclasses FcγRII and FcγRIII in the activation of human neutrophils by low and high valency immune complexes
Authors: Strohmeier Gregg R , Brunkhorst Beatrice A , Seetoo Kurt F , Meshulam Tova , Bernardo John , Simons Elizabeth R 
Published: January 2018

Abstract
Two Fcγ receptor (FcγR) subclasses on human neutrophils, FcγRII and FcγRIII, activate different cellular functions. To examine the involvement of each receptor subtype in polymorphonuclear leukocyte activation, Fab and F(ab’)2 fragments of subclass-specific monoclonal antibodies ([mAbs] mAb IV.3 against FcγRII and mAb 3G8 against FcγRIII, respectively) were used to block the binding of low valency immune complexes (LICs) and high valency immune complexes (HICs). Flow cytometry then permitted the simultaneous quantitation of antibody and ligand binding, the elicited intracellular Ca2+ concentration (Δ[Ca2+]int), initiation of the oxidative burst, and/or the phospholipase A activation in the same cell. We have previously demonstrated that subsaturating dosages of HIC bind uniformly to all the cells but elicit an “all-or-none” (i.e., dose independent) maximal Δ[Ca2+]int in a dose-dependent subpopulation of the cells. In contrast, both the proportion of cells responding and the magnitude of the Δ[Ca2+]int transient depend on the subsaturating dose of LIC, even though it too binds uniformly to all the cells, nonresponding as well as responding. These earlier findings have here been extended by single cell flow cytometric analysis to demonstrate that F(ab’)2 FcγRIII is the major FcγR involved in HIC binding (and [Ca2+]int mobilization), as well as in oxidative burst and phospholipase A activation. In contrast, both receptor subclasses must be available for LIC-elicited Δ[Ca2+]int, as blockage by either of the mAb Fab or F(ab’)2 fragments abrogates this response, even though LIC binding to the receptors is not decreased. Furthermore, LIC elicited little oxidative burst activity and failed to activate phospholipase A but cross-linking to achieve multivalency, previously shown to induce [Ca2+]int and oxidative burst responses, elicited phospholipase A activity via FcγRIII. FcγRII’s role appears to be modulation of the small, late Ca2+ influx observed at &gt; 1 min, whereas FcγRIII modulates all the earlier larger events. Thus, simultaneous observation of receptor identity, receptor occupancy, and consequent activation parameters in the same cell by flow cytometry permits use to demonstrate that FcγRII is necessary for the small signal transduction elicited by LIC; it plays a relatively small role in polymorphonuclear leukocyte stimulation by HIC. FcγRIII is the main receptor responsible for immune complex-elicited polymorphonuclear leukocyte responses; its efficacy is greatly enhanced when the receptors are cross-linked, either by preequilibrated multivalent complexes or by in situ cross-linking of bound LIC with excess antibody.