bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Neutrophil Functions by Platelets and Platelet-Derived Products: Description of Multiple Inhibitory Properties
Authors: McGarrity S T , Hyers T M , Webster R O 
Published: January 2018

Abstract
The effect of platelets and their products on in vitro responses of human neutrophils to f-met-leu-phe (fMLP) and phorbol myristate acetate (PMA) was studied. Platelets produced a concentration-dependent inhibition of neutrophil superoxide anion (O2-) generation with maximum inhibition of the response to fMLP approaching 42.2 ± 5.4% and that to PMA approaching 85.9 ± 3.4%. Supernates of thrombin-activated platelets produced maximal inhibition of neutrophil O2- generation in response to fMLP (66.3 ± 4.2%) at a ratio of 10 platelet equivalents (PEQ) to 1 neutrophil but failed to affect the cells’ response to PMA. In contrast, lysate of sonicated platelets Inhibited neutrophil O2- generation in response to both fMLP (59.6 ± 2.0%) and PMA (90.1 ± 1.3 %). Biochemical characterization of platelet lysate identified at least two stimulus-specific inhibitory activities which differ in size, thermal stability and enzyme sensitivity. Platelet lysate also maximally inhibited neutrophil degranulation and chemotaxis at a ratio of 20 PEQ to 1 neutrophil. Our findings indicate that physiologically achievable levels of platelets or their products modulate the response of neutrophils in a stimulus-specific manner and are thereby capable of potentially limiting tissue damage which accompanies neutrophil activation during inflammation.
Induction of Adenosine Deaminase and 5′ Nucleotidase Activity in Cultured Human Blood Monocytes and Monocytic Leukemia (THP-1) Cells by Differentiating Agents
Authors: Murray James L , Mehta Kapil , Lopez-Berestein Gabriel 
Published: January 2018

Abstract
The in vitro effect of short-term culture as well as the effect of retinol (ROH), retinoic acid (RA), muramyl dipeptide ([Abu']MDP), lipopolysaccharide (LPS), and gamma interferon (IFN-γ) on the induction of the purine metabolic enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5′nucleotidase (5NT) in human peripheral blood monocytes (HPBM) was examined. HPBM isolated by centrifugal elutriation were cultured for up to 96 h. Following an initial time lag of 24 h, mean ADA activity from seven separate experiments as measured in nmoles/106 cells/h increased from a baseline of 31.3 ± 9.3 to 57.8 ± 16.4 (P &lt; 0.005) at 72 h and to 72 ± 21.5 (P &lt; .025) by 96 h. 5NT activity increased from a baseline of 2.2 ± 0.9 to a maximum of 44 ± 10.1 by 72 h and then declined to 29 ± 18 (P &lt; 0.005) by 96 h, while no significant change in PNP activity was observed. HPBM incubated for 3 d with optimal concentrations of LPS, RA, and IFN-γ had increases in ADA and 5NT activity ranging from three- to 10-fold compared to HPBM cultured in media alone, whereas no effect was observed with ROH and [Abu']MDP. RA, but not ROH, significantly enhanced ADA activity in a monocytic leukemia cell (THP-1) line. Addition of RA or the tumor promoter, phorbol 12-myristic 13-acetate (PMA), to HPBM or THP-1 cells resulted in significant increases in 5NT activity with opposite effects on ADA activity. These findings suggest that the biological mechanisms associated with differentiation in normal and malignant monocytes seem to be related and that the sequence and degree to which the various differentiation agents induce the enzyme elevations are also related to the mechanisms of activation/differentiation.
Nonspecific and Candida-Specific Immune Responses in Mice Suppressed by Chronic Administration of Anti-μ
Authors: Kuruganti Uma , Henderson Lee A , Garner Ronald E , Asofsky Richard , Baker Phillip J , Domer Judith E 
Published: January 2018

Abstract
CBA/J mice were immunosuppressed by repeated administration of goat antibody specific for μ chain of immunoglobulin M (IgM) and tested for nonspecific and Candida albicans-specific immune responses. Immunosuppression was demonstrated by a dramatic reduction in the number of antibody-forming cells in the spleens of anti-μ-treated mice when immunized with sheep erythrocytes, by greatly reduced in vitro responsiveness of both spleen and lymph node lymphocytes from anti-μ-treated mice to lipopolysaccharide, and by a large reduction in the number of splenic IgM-posttive cells. T cell function, on the other hand, appeared to be relatively unaltered in anti-μ-treated animals, in the cytotoxic T lymphocyte activity against an allogeneic target was similar in splenocyte cultures from anti-μ- and mock-treated animals, and splenic and lymph node lymphocytes proliferated in response to concanavalin A in a lymphocyte stimulation assay. Moreover, Candida-specific delayed hypersensitivity to two different Candida antigens, one cell wall-derived (GP) and the other cell membrane-derived (BEX), was of comparable intensity in immunosuppressed and normal animals. When anti-μ- and mock-treated mice were immunized by the cutaneous inoculation of viable C. albicans blastospores and then challenged intravenously to assess the development of protective immunity, only mock-treated animals, male and female, had significant (p ≤ 0.05) protective responses demonstrable by reduction in the number of colony-forming units cultured from their kidneys 28 days after intravenous challenge. If consideration was given to the number of animals which had cleared Candida completely from the kidney, however, there appeared to be protective responses operative in the female anti-μ-treated animals as well. Neither anti-μ-treated males nor females, when immunized and challenged with C. albicans, produced Candida-specific antibody detectable by counte-rimmunoelectrophoresis, whereas all immunized and challenged mock-treated animals produced antibody. The data are consistent with the hypothesis that anti-μ treatment has little effect on multiple cellular immune functions, including those specific for C. albicans, and the combination of antibody, cell-mediated immunity and innate defenses are responsible for solid systemic defense against the fungus.
Are Serine Proteases Involved in Immune Complex Activation of Neutrophils?
Authors: Mark Deiren E , Lazzari Kristina G , Simons Elizabeth R 
Published: January 2018

Abstract
Soybean polypeptides and diisopropylfluorophosphate (DFP) have been reported to inhibit neutrophil functions such as the oxidative buret, chemotaxis, and/or phagocytosis in response to soluble stimuli; these observations would be compatible with the involvement of an active serine protease in neutrophil stimulation. We have investigated the possibility of such involvement when particulate stimuli such as immune complexes are utilized. The depolarization of the neutrophils’ membrane potential, one of the earliest indicators of stimulation, and superoxide production, which is detectable 30-45 sec later, were our indicators of neutrophil response to immune complexes. The neutrophils were equilibrated with, and after 5 min washed free of, up to 60 mM DFP, a potent covalent serine protease inhibitor. At DFP concentrations below 24 mM, such treatment did not perturb neutrophil activation as measured by either of the above parameters, nor did F- alone under comparable conditions. Additionally, the immune complex induced responses of neutrophils preincubated for 3 min with N-α-p-tosyl-L-lysine chloromethylketone (TLCK), L-1-tosylamido-2-phenyl-ethyl-chloromethylketone (TPCK), or phenyl-methyl-sulfonyl-fluoride (PMSF), covalent serine protease inhibitors which have, however, been shown to function in other capacities, e.g., as superoxide dismutases; 1 mM PMSF or 0.5 mM TLCK consistently reduced the observed membrane depolarization, one of the earliest consequences of neutrophil activation, by 20-30%, while 0.I mM TLCK and 0.01 mM TPCK had little or no effect. The inhibition of superoxide production, a slightly later stimulus response, by PMSF, TLCK, and TPCK was more profound (50-75%); these compounds have, however, been shown to have activities other than serine protease inhibitors—for example, as superoxide dismutases. Since DFP is purely a serine protease inhibitor, and since the three other compounds do not affect depolarization (the earlier and superoxide independent event), our results indicate that active serine proteases do not appear to be necessary for immune-complex-initiated neutrophil stimulation. Other stimuli, which are known to activate neutrophils by different pathways, were not investigated.
Graunulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (CSF-1) Synergize to Stimulate Progenitor Cells With High Proliferative Potential
Authors: Falk Lydia A , Vogel Stefanie N 
Published: January 2018

Abstract
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland The ability to expand a population of bone marrow progenitors capable of forming macrophage colonies of high proliferative potential (HPP-CFC) was achieved using a culture system and signal requirements not previously shown to support the growth of HPP-CFC. Using bone marrow cells from untreated animals (not 5-FU-treated), culture conditions designed primarily for the detection of GM-CFC or M-CFC progenitors, and a more stringent criteria for HPP-CFC colony size (≥ 2 mm diameter), HPP-CFC progenitor expansion was demonstrated following simultaneous addition of rGM-CSF and CSF-1 to bone marrow cultures. Examination of the sequence and temporal requirements for rGM-CSF and CSF-1 addition necessary for the development of HPP-CFC-like colonies revealed that addition of the second factor could be delayed for up to 5 days and still result in the development of significant numbers of HPP-CFC colonies. Based on a comparison with human spleen cell conditioned medium (HSCM) and interleukin 1 (rIL 1), as sources of “synergistic activity” (SA) for the development of HPP-CFC-like colonies in combination with CSF-1, the combination of GM-CSF and CSF-1 appears to represent a novel pathway for stimulating the expansion of HPP-CFC progenitors with high proliferative potential.
Synergistic Interactions Between IFN-γ and IFN-β in Priming Murine Macrophages for Tumor Cell Killing
Authors: Pace Judith L 
Published: January 2018

Abstract
The ability of MulFN-β and MulFN-γ to potentiate the development of tumoricidal activity in proteose peptone-elicited murine peritoneal macrophages was investigated. Macrophages were stimulated with increasing concentrations of either MulFN-β or MulFN-γ, alone and in combination, in the presence of 1 ng/ml lipopolysaccharide (LPS). The priming activities attributable to the interferons (IFNs) were quantified using the dose-response curves obtained for these samples. The priming activity observed for mixtures of MulFN-β and MulFN-γ was greater than that expected if MulFN-β and MulFN-γ had acted in an additive manner. Isobologram analysis of data obtained when macrophages were stimulated with combinations of IFNs demonstrated that MulFN-β and MulFN-γ acted synergistically to prime macrophages for tumor cell killing. The greatest degree of synergy was observed when macrophages were stimulated with suboptimal and nearly equivalent concentrations of each class of IFN. Further studies demonstrated that macrophages stimulated with combinations of MulFN-β and MulFN-γ were more sensitive to the trigger signal provided by LPS than were cells primed with either IFN alone. Thus, the synergistic effects observed were quantitative in nature in that macrophages perceived combinations of MulFN-β and MulFN-γ as having higher priming activities than expected.
Interleukin-1 and Interleukin-6 Stimulate Acute-Phase Protein Production in Primary Mouse Hepatocytes
Authors: Prowse Karen R , Baumann Heinz 
Published: January 2018

Abstract
Primary mouse hepatocytes were treated with the acute-phase mediators interleukin-1, Interleukin-6, and glucocorticoids, singularly and in combination, in order to delineate the spectrum of proteins induced by the stimulatory factors. As found for rat and human liver cells, mouse hepatocytes responded to the cytokines by increasing production of acute-phase proteins, which in mice include haptoglobin, α1-acid glycoprotein, complement C-3, serum amyloid A, and hemopexin. Serum amyloid A was unusual in that only the acidic peptide form responded to treatment with IL-1 and IL-6; the more basic form remained unchanged. In addition, an unidentified secretory protein was induced only by mixtures containing IL-6. The present study shows that a combination of IL-1, IL-6, and glucocorticoids is required for regulation of acute-phase plasma protein production in mouse liver cells.
In Vivo Neutrophil Emigration in Response to Interleukin-1 and Tumor Necrosis Factor-Alpha
Authors: Mason Margaret J , van Epps Dennis E 
Published: January 2018

Abstract
The migration of polymorphonuclear leukocytes (PMN) in response to recombinant interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF), C5a, and f-met-leu-phe-lys (FMLPL) in vivo was studied using a mouse subcutaneous sponge implantation model. In this model sponges were implanted in C3H/OUJ mice, and 2 days later they were injected with the test sample. After varying times, sponges were removed and digested with collagenase, and total cell counts and differentials were enumerated. IL-1 was found to stimulate a significant influx of PMN, which peaked at 6 hr and declined to near baseline levels by 24 hr. This response was dose-dependent, with the greatest response observed when 5 units of IL-1 were injected. When the IL-1 concentration was increased to 10 U, the total number of PMN migrating into the sponge was decreased, compared with that observed with 5 U of IL-1. The overall number of PMN migrating into the sponge 6 hr after injecting 5 U of IL-1 averaged 269% of the number of PMN migrating randomly into the sponge. No difference in the total number of macrophages or lymphocytes in control or IL-1-injected sponges was observed in this time frame. Heat treatment of the IL-1 at 90°C for 30 min ablated the response. Similar studies with TNF and C5a showed that both of these agents also stimulated an influx of PMN that peaked 6 hr postinjection. In contrast, FMLPL did not stimulate a PMN response. When IL-1 and TNF were injected simultaneously, an additive response was observed. These data indicate that IL-1, TNF, and C5a can all stimulate a PMN response in vivo and support the hypothesis that these substances are actively involved in the mobilization of PMN to inflammatory sites in vivo.
Comparative Study of Cytotoxicity, Tumor Necrosis Factor, and Prostaglandin Release After Stimulation of Rat Kupffer Cells, Murine Kupffer Cells, and Murine Inflammatory Liver Macrophages
Authors: Decker Thomas , Lohmann-Matthes Marie-Luise , Karck Ulrich , Peters Thomas , Decker Karl 
Published: January 2018

Abstract
Macrophages (MØ) and MØ-depleted (nonadherent) nonparenchymal cells (NPC) of the liver were examined for their cytotoxic potential against tumor cells, production of tumor necrosis factor (TNF), and release of prostaglandins (PG) following stimulation by lipopolysaccharide (LPS), interferon-γ (IFNγ), and zymosan.
Resident murine liver macrophages had no natural cytotoxicity for the TNF-resistant target cell line P815. Activation of these cells was only obtained by a combination of IFNγ and LPS. Inflammatory murine macrophages were in a primed stage and could be activated by LPS alone in the absence of IFNγ. Rat resident macrophages resembled functionally the inflammatory macrophages of the mouse liver rather than the resident macrophages. They displayed natural cytotoxicity against all targets tested and were further activated by LPS in the absence of IFNγ. Similar results were obtained with respect to macrophage-depleted nonadherent NPC: Mouse NPC had a low level of NK activity against Yac-1 cells. Treatment with pyran copolymer resulted in a strong increase of cytotoxicity against Yac-1; furthermore, a TNF-dependent killing of Wehi 164 and TNF-independent cytotoxicity against P815 cells were now acquired. In the rat NPC prepared from unstimulated animals expressed high levels of natural cytotoxicity against all targets.
No major differences could be observed between inflammatory MØ and Kupffer cells of rat and mouse liver with regard to TNF production and TNF-dependent killing of Wehi 164 tumor cells. The same was true for the spectrum of secreted prostanoids. Upon activation of all cell populations a marked shift toward the production of PGE2 occurred. Experiments involving the cyclooxygenase inhibitor indomethacin showed enhanced TNF-dependent tumor cell killing by nonactivated MØ in the absence of prostanoid production.
Neutrophil Membrane Sulfhydryl Groups Are Involved in Stimulated Neutrophil Adherence to Endothelium
Authors: Schwartz Barbara R , Harlan John M 
Published: January 2018

Abstract
We investigated the role of membrane sulfhydryl groups in adherence of stimulated polymorphonuclear neutrophils to cultured endothelial cells. Treatment of neutrophils with p-chloromercuriphenyl sulfonate (PCMPS), a slowly penetrating sulfhydryl reagent, inhibited phorbol myristate acetate (PMA)- or calcium ionophore A23187-stimulated adherence to cultured human or bovine endothelial cells. At concentrations which completely blocked PMA-stimulated adherence, PCMPS did not cause release of lactic dehydrogenase, inhibit PMA-mediated degranulation or hydrogen peroxide production, or prevent the PMA-induced increased surface expression of CD11b/CD 18 (Mac-1). Coincubation with a competing reduced sulfhydryl compound protected neutrophils from inhibition of PMA-stimulated adherence by PCMPS, whereas coincubation with an oxidized sulfhydryl compound did not. Monobromotrimethylammoniobimane, a nonpenetrating sulfhydryl reagent that is structurally unrelated to PCMPS, also inhibited stimulated neutrophil adherence to endothelium cultures. We conclude that stimulated neutrophil adherence to endothelium involves neutrophil membrane protein sulfhydryl groups.
Effect of Interleukin 1 on the Induction and Maintenance of B Cell Tolerance In Vitro
Authors: Duan Ji-Ming , Habicht Gail S 
Published: January 2018

Abstract
The effects of interleukin 1 (IL-1) on induction and maintenance of immune tolerance in vitro have been studied by using splenocytes from C57BL/6 male mice. B cell tolerance to the hapten trinitrophenol (TNP) was induced with TNP-human gamma globulin (HGG) and the cells were challenged with TNP-Ficoll. To determine the tolerance (or immunity), antibody concentrations in the supernatant fluids were measured by using a TNP-specific ELISA assay. Partially purified murine IL-1 abrogated tolerance induction, and when it was added at challenge phase, it also abrogated tolerance. In addition, partially purified IL-1 converted TNP-HGG from a tolerogen into an immunogen without any additional exposure to antigen. Similar results were obtained when recombinant human IL-1 α was used in place of partially purified natural IL-1. IL-1 is most likely acting directly on B cells rather than through the agency of T cells because purified B cells failed to become tolerant in the presence of IL-1. Studies of IL-1 production by antigen- or tolerogenstimulated splenocytes or purified B cells showed that only antigen could elicit IL-1 production in these cells. That tolerance abrogation is unique to IL-1 is suggested by studies which show that TNF, IL-2, and INF γ, alone, in combination with each other, or in combination with subeffective concentrations of IL-1 failed to effect tolerance abrogation.
Binding of Metastatic Colon Carcinoma Cells to Liver Macrophages
Authors: Gjøen Tor , Seljelid Rolf , Kolset Svein Olav 
Published: January 2018

Abstract
The liver is frequently colonized by metastatic tumor cells despite its dense population of macrophages (Kupffer cells). We have studied the interactions between metastatic colon carcinoma cells (DHD) and syngeneic Kupffer cells under different experimental conditions in vitro. In an adhesion assay the binding of DHD cells to Kupffer cell monolayers was shown to be time and temperature dependent, reaching a maximum level after about 90 min of incubation at 37°. in contrast, only a low level of binding could be observed at 4°. The level of binding could be increased by pretreatment of the Kupffer cells with phorbol 12-myristate 13-acetate. A firm interaction between the two cell types was shown to be dependent on the presence of calcium- and trypsin-sensitive structures on the surface of the Kupffer cells. Pretreatment of the macrophages with the cytoskeletal inhibitors colchicine and cytochalasin B was also found to reduce significantly the binding of tumor cells. This binding was also inhibited to a large extent by D-mannose and N-acetyl-D-galactosamine. The Kupffer cells were not cytotoxic against the colon carcinoma cells.
Structural Alterations in Fibroblast Monolayers Caused by Mast Cell Degranulation
Authors: Ginsburg Haim , Amira Milly , Padawer Jacques , Davidson Sima 
Published: January 2018

Abstract
Populations of mature, long-lived, nondividing mast cells develop on embryonic fibroblast monolayers after 1 mo growth of lymph node cells taken from mice immunized with horse serum. Total mast cell degranulation with 80-90% histamine release has been obtained by monoclonal anti-2,4-dinitrophenol (anti-DNP) IgE and the antigen. This degranulation process was studied by time-lapse cinematography and scanning electron microscopy. Excitation of the mast cells began as early as 10 s after addition of the antigen and lasted for about 15 s. Consequently, the fibroblast cytoplasm was displaced by short 5-10 s movements. Before degranulation, due to an extracellular film that coated the cells and the extracellular fibers, the monolayer appeared as a continuous, uninterrupted layer. After degranulation and fibroblast cytoplasm displacement, the fibrous network was exposed. Several inhibitors and antagonists of mast cell mediators were introduced to the cultures prior to addition of the antigen. So far, only with soybean trypsin inhibitor was the cytoplasm dislocation inhibited. Histamine H1 and H2 and serotonin receptor antagonists, as well as indomethacin, Cortisol, aprotinin, and phenylmethylsulfonyl fluoride, did not inhibit. These results suggest that chymase, which constitutes the greater part of the mast cell granule protein, is the causative agent.
Thermal Regulation of FMLP Receptors on Human Neutrophils
Authors: Coles Rosalind B , Ranney Richard R , Freer Richard J , Carchman Richard A 
Published: January 2018

Abstract
Polymorphonuclear leukocytes (PMNs) from subjects diagnosed as having iuvenile periodontitis (JP) have been categorized on the basis of their chemotactic (CTX) response to f-met-leu-phe (FMLP) when assayed concurrently with PMNs from periodon-tally healthy subjects (HP). When PMNs from JP groups demonstrating depressed CTX were assayed for lysosomal enzyme secretion (LES) in response to FMLP, there were no significant differences with respect to rate or amount. Significant differences were observed between HP and chemotactically depressed JP cells when assessed for FMLP receptor ligand binding at 23°, but not at 4°. Receptor differences observed at 23° in HP cells included an increase in amount of total binding, number of receptors, and available dispiaceable binding sites, compared with the chemotactically depressed JP PMNs, whereas the receptor affinities were similar. These data suggest that differences in FMLP receptor density in JP PMN that are chemotactically depressed may be related to processes that modulate receptor mobility and/or expression.