bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of Interferon-Gamma and Tumor Necrosis Factor by Legionella pneumophila: Augmentation of Human Neutrophil Bactericidal Activity
Authors: Blanchard D Kay , Friedman Herman , Klein Thomas W , Djeu Julie Y 
Published: January 2018

Abstract
We have previously reported that Legionella pneumophila antigens can induce inter-feron-gamma (IFN-gamma) and tumor necrosis factor (TNF) in vitro and in vivo in mice. Furthermore, treatment of murine polymorphonuclear leukocyte (PMN) cultures with these cytokines resulted in augmented killing of the bacteria in vitro. The purpose of the present study was to determine if these findings could be extended to human responses. Here we report that Legionella antigens induced IFN-gamma and TNF in nonimmune human leukocytes cultures, and that these cytokines were able to stimulate the bactericidal activity of isolated PMN against L. pneumophila in vitro. Furthermore, optimal production of IFN-gamma was found in cultures which were enriched for large granular lymphocytes (LGL). The phenotype of IFN-producing cells was determined to be CD11 +, CD16+, CD2+, and negative for CD4, CD8, CD14, and Leu 7. Additionally, Legionella-infected monocytes were found to produce TNF in a dose-dependent response to the number of infecting bacteria, and the addition of recombinant IFN-gamma to infected monocytes resulted in augmented production of TNF in a synergistic manner. Finally, treatment of PMN with recombinant IFN-gamma and recombinant TNF augmented their bactericidal activity against Legionella in a dose dependent response. Thus, cytokines which can be induced by L. pneumophila antigens are able to stimulate PMN function in vitro, suggesting that resistance to infection results from a complex interaction of cytokines and cell responses.
Hematologic Interactions of Endotoxin, Tumor Necrosis Factor Alpha (TNFα), Interleukin 1, and Adrenal Hormones and the Hematologic Effects of TNFα in Corynebacterium parvum-Primed Rats
Authors: Ulich Thomas R , del Castillo Juan , Ni Rong-Xiang , Bikhazi Nadim 
Published: January 2018

Abstract
Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose response-dependent initial neutropenia followed by a monophaslc neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophaslc neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-Induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte macrophage system and treated with TNF differed from naive rats treated with TNF in that the second peak was as great as the initial peak of neutrophilia, supporting the hypothesis that the second peak of TNF-induced neutrophilia is due to the release of endogenous monokines. In conclusion, exogenous TNF, IL-1, and adrenal hormones affect circulating numbers of lymphocytes and neutrophils in a fashion consistent with their postulated endogenous role in the regulation of leukocyte trafficking during bacterial infection.
Natural Killer Cell Function in Patients With Acquired Immunodeficiency Syndrome and Related Diseases
Authors: Brenner Bluma G , Dascal André , Margolese Richard G , Wainberg Mark A 
Published: January 2018

Abstract
This review describes current knowledge of changes in natural killer (NK) cell function in acquired immunodeficiency syndrome (AIDS)-related disorders, vis-à-vis associated abnormalities in NK cytolytic function, NK cell subset distribution, NK cytopathology, and lymphokine regulation. NK cells, which are closely associated with large granular lymphocytes, are spontaneously cytotoxic to tumor and virally infected targets. As such, they may play a role in natural resistance to human immunodeficiency virus type 1 (HIV-1)-associated disorders and other opportunistic infections. Yet, peripheral blood NK activity is frequently reduced in patients with HIV-1-induced disease. NK cells are heterogeneous both with respect to their expression of serologically defined membrane antigens and functional activity. In AIDS-related syndromes, there appears to be a diminution of the NK pool (CD16+ cells) involved in cytolytic function, while there is an elevation of the NK pool that coexpresses NK (Leu 7+) and T (CD8+) cell markers, which show little or no involvement in cytolytic function. The impairment of in vitro NK function is not associated with a reduced frequency of lytic conjugates of effectors and target cells nor with the recycling capacity of these effector cells but rather is associated with defects in the NK cell lytic machinery following formation of such conjugates. NK cells in AIDS patients show an impairment in effector cell microtubule rearrangement following target cell interaction. The causes of NK cell dysfunction in AIDS-related disorders remain unknown. NK cells do not appear to express the CD4 epitope of the HIV receptor, nor have they been demonstrated to be susceptible to infection by HIV-1. There appears to be a preponderance of immature NK cells and a lymphokine imbalance in patients with HIV-1 associated disease. Interleukin-2 can partially restore diminished in vitro NK function. Elucidation of the involvement of the NK compartment in natural resistance to HIV-1 merits further investigation.
Chemiluminescence in a Macrophage Cell Line Modulated by Biological Response Modifiers
Authors: Tosk Jeff , Lau Benjamin H S , Lui Paul , Myers R Craig , Torrey Robert R 
Published: January 2018

Abstract
We have studied a murine macrophage cell line, J774, and found these cells capable of a zymosan-triggered chemiluminescent oxidative burst. Such activity was enhanced by preincubation with Corynebacterium parvum (CP), bacillus Calmette-Guerin, and Iipopolysaccharide (LPS). Under similar conditions, CP and LPS were shown to enhance J774-mediated tumor cell lysis. We have also demonstrated that murine interferon α + β rendered J774 cells more sensitive to the actions of CP and LPS. These results indicate that J774 cells may be useful for the in vitro evaluation of biological response modifiers as well as the study of oxygen radical production by macrophages.
Functional Analysis of Monocyte-Macrophages Derived From Nonadherent Cord Blood Progenitor Cells: Correlation With the Ontogeny of Cell Surface Proteins
Authors: Santiago-Schwarz Frances , McHugh Donna M , Fleit Howard B 
Published: January 2018

Abstract
In this study we examine some of the phenotypic and functional characteristics that accompany the differentiation of monocyte-macrophages from nonadherent precursors present in cord blood. Class II major histocompatibility complex (MHC) molecules identified by monoclonal antibody (mAb) L243 were the earliest monocyte-macrophage-associated antigens to be expressed. CD14 molecules, identified by mAb MO.2, and the transferrin receptor, identified by mAb OKT9, increased linearly over the 21-day culture period. In contrast, FcγR were not expressed on these cells until 14 days of culture. FcγRI was present on approximately 80% of the cells, whereas FcγRII and FcγRIII were present on 30% and 20% of the cells, respectively.
Functional activity of the nonadherent cell-derived monocyte-macrophages paralleled the phenotypic maturation of these cells. The capacity to stimulate a mixed leukocyte reaction paralleled the expression of class II MHC molecules. Similarly, the capacity to phagocytose Escherichia coli and Staphylococcus aureus paralleled the appearance of CR3. Indeed, phagocytosis of these organisms was partially blocked by mAb OKM-1. These studies demonstrate that monocyte-macrophages derived from cord blood nonadherent mononuclear cells are a useful population with which to characterize human macrophage differentiation and functional and phenotypic heterogeneity.
Proliferation of Macrophage Subpopulations in the Adult Rat: Comparison of Various Lymphoid Organs
Authors: Westermann Jürgen , Ronneberg Sabine , Fritz Franz Joachim , Pabst Reinhard 
Published: January 2018

Abstract
Adult male Lewis rats received a single intravenous injection of 5-bromo-2′-deoxyuridine (BRDU) to label all proliferating cells in the S-phase of the cell cycle. Various lymphoid organs were removed 1 and 24 hr after injection to assess local proliferation and migration of newly formed cells, respectively. In ceil suspensions, surface staining was performed for macrophage subsets (ED1, ED2, ED3), and the DNA label BRDU was detected by a monoclonal antibody. Local proliferation of ED1+ macrophages occurred in all organs investigated with the exception of the blood. Bone marrow outweighed the other organs by far; in addition to the proliferating ED1+ promonocytes, the bone marrow also contained BRDU-labeled ED2+ macrophages. Newly formed ED1+ monocytes migrated into lymphoid organs such as the mesenteric lymph nodes and spleen where they comprised about 90% of newly formed macrophages. In the spleen, ED3+ macrophages seemed to be renewed by local proliferation, whereas in the mesenteric lymph nodes these cells were replaced by immigration. The heterogeneity of macrophages was further demonstrated by the different renewal of splenic macrophages. ED1+ and ED3+ cells were replaced in a matter of days, whereas it would probably take several months to renew ED2+ cells.
Studies of the Mechanism of Natural Killer (NK) Degranulation and Cytotoxicity
Authors: Atkinson Eric A , Gerrard Jon M , Hildes G Elske , Greenberg Arnold H 
Published: January 2018

Abstract
Exocytosis of cytotoxic granule contents towards bound target cells is thought to be of central importance in natural killer (NK) cell-mediated killing. Although cellular cytotoxicity involving degranulation is thought to be calcium-dependent, the biochemical mechanisms that mediate this granule mobilization are unknown. Inositol-1,4,5-tris-phosphate (IP3), which acts to elevate internal calcium levels, and 1,2-diacylglycerol (DAG), which activates protein kinase C, are potent second messengers that have been shown to synergistically mediate secretion in other cell types. Production of these products of inositol phospholipid metabolism has previously been demonstrated in a rat NK cell line RNK upon exposure to susceptible tumor targets. We therefore Investigated the role of IP3 and DAG in NK-mediated cytotoxicity, specifically at the level of degranulation. Pretreatment of RNK cells with neomycin, a drug that interferes with the hydrolysis of inositol phospholipids and thus inhibits the formation of second messengers, inhibited RNK cytotoxicity against a susceptible tumor target and also inhibited RNK production of DAG in response to a similar target Natural killing exhibited by normal rat nylon wool-nonadherent spienocytes was also inhibited by neomycin. Phorbol-12-myristate,13-acetate (PMA), a phorbol ester that acts like DAG to activate protein kinase C, markedly enhanced lysis of a susceptible target cell by RNK. We evaluated whether modulation of lysis by these drugs was associated with effects on RNK degranulation by assaying the release of a granule-specific serine esterase (BLTE) in response to PMA and the calcium ionophore A23187. These agents synergized to promote the release of BLTE, and the extent of release was dependent on the concentrations of both agents. D2O and cytochalasin B, which enhance secretion in other cells, both enhanced BLTE release from RNK cells, indicating that we were detecting BLTE released via granule secretion and not due to nonspecific causes such as cell lysis. Our findings lead us to propose that NK cells form IP3 and DAG in response to susceptible target cells and that a major function of these second messengers is to mediate the exocytosis of cytotoxic granules towards the bound target cells.
Antigen Presentation by the CD4 Positive Monocyte Subset
Authors: Szabo G , Miller C L , Kodys K 
Published: January 2018

Abstract
Although CD4 antigen is expressed on monocytes (MØ), its functional role is uncharacterized. In this study, isolated human MØ were separated into CD4+ and CD4- MØ subsets and assessed for presentation of tetanus toxoid. The CD4- MØ subset had decreased antigen presenting cell (APC) capacity as well as increased PGE2 production when compared to the CD4+ MØ subset. Addition of a cyclo-oxygenase inhibitor (Indo-methacin) did not restore the CD4- MØ subset's APC capacity to that of the similarly treated CD4+ MØ subset, eliminating differential PGE2 production as the primary cause of differential APC capacity. Production of monokines such as IL-1 and plasminogen activator, which affect APC capacity, was similar in the CD4 MØ subsets. However, tumor necrosis factor (TNF) production (IFNγ plus MDP-induced) of the CD4+ MØ subset was slightly greater than that of the CD4- MØ. CD4- MØ's lower APC capacity is not totally explained by their differential IL-1, TNF, or PGE2 production.
Immune Dysfunction Expressed Selectively on L3T4+ T Cells in the Tumor-Bearing State
Authors: Tada Tsuyoshi , Sano Haruo , Sato Soichiro , Shima Junko , Fujiwara Hiromi , Hamaoka Toshiyuki 
Published: January 2018

Abstract
Spleen cells from normal C3H/He or BALB/c mice generate cytotoxic T-lymphocyte (CTL) responses to both trinitrophenyl (TNP)-modified syngeneic cells (TNP-self) and allogeneic cells. In contrast, cells from these strains of mice bearing a syngeneic tumor failed to induce anti-TNP-self-CTL responses, although portions of the same responding cells generated comparable anti-allo-CTL responses to those induced by normal responding cells. Although anti-allo-CTL responses were inducible from only Lyt-2+ T-cell subset of responding cells from normal or tumor-bearing mice, induction of TNP-CTL responses required the participation of L3T4+ T-cell subset as well as Lyt-2+ CTL precursors. In addition, the fact that the addition of concanavalin A-stimulated culture supernatant to cultures of responding cells from tumor-bearing mice resulted in the induction of appreciable anti-TNP-self CTL responses demonstrated the defect of L3T4+ T-cell function in the tumor-bearing state. Such a functional defect was ascribed neither to the loss of L3T4+ T cells nor to the generation of suppressor cells in spleen cells of tumor-bearing mice. It was found on one hand that in vitro stimulation of antigen-presenting cell (APC)-depleted normal responding population with TNP-self prepared from cells of normal or tumor-bearing mice produced comparable anti-TNP CTL responses. On the other hand, APC-depleted responding cells from tumor-bearing mice were unable to induce anti-TNP CTL responses under conditions in which APC-depleted normal responding cells induced an effective TNP-CTL response. These results indicate that selective impairment of L3T4+ T cell-mediated immunity is induced in the tumor-bearing state and that such an impairment is ascribed to the dysfunction of L3T4+ T cells themselves, but not of APC required for the activation of L3T4+ T-cell subset.
Activation of Neutrophils by Cachectin/Tumor Necrosis Factor: Priming of N-Formyl-Methionyl-Leucyl-Phenylalanine-Induced Oxidative Responsiveness Via Receptor Mobilization Without Degranulation
Authors: Tennenberg Steven D , Solomkin Joseph S 
Published: January 2018

Abstract
Human recombinant cachectin/tumor necrosis factor (TNF) was shown to prime neutrophils (PMNs), in a dose-dependent fashion, for subsequent oxidative responsiveness toward n-formyl-methionyl-leucyl-phenylalanine (FMLP). One basis for this phenomenon appeared to be TNF-mediated FMLP receptor mobilization. The maximal observed priming response was associated with a nearly twofold increase in the expression of PMN FMLP surface receptors, without changes in receptor affinity. Priming was not seen following stimulation with phorbol myristate acetate, possibly eliminating a role for the protein kinase C-dependent transductional components of FMLP-induced oxidative activity in the priming process. FMLP receptor mobilization occurred without significant degranulation as evident by an absence of increased granular enzyme release. These data support a potential role of macrophage-derived TNF in the augmentation of PMN host-defense during infectious and inflammatory challenge. TNF-mediated PMN oxidative priming may also promote oxidant tissue injury as seen in septic shock, adult respiratory distress syndrome, and multiple system organ failure.
Effect of Idarubicin and Epirubicin on In Vitro Polymorphonuclear Function: Diminished Superoxide Radical Formation Compared to Their Parent Compounds Daunorubicin and Doxorubicin
Authors: Cairo Mitchell S , Toy Cynthia , Sender Leonard , van de Ven Carmella 
Published: January 2018

Abstract
Anthracyclines are active against a variety of malignancies. The present study examined the effect of epirubicin and idarubicin on in vitro polymorphonuclear (PMN) function including chemotaxis, aggregation, bacteriocidal activity degranulation, and superoxide generation. We also studied the effects of cyclosporin (100 ng/ml) and verapamil (500 ng/ml), two membrane active biological response modifiers, on their potential role in modulating anthracycline-induced oxygen radical formation in the human PMN. Older anthracyclines (doxorubicin and daunorubicin) did not affect superoxide generation in the human PMN. However, the newer anthracyclines, both epirubicin and idarubicin, profoundly inhibited human superoxide generation (P &lt; .02) and (P &lt; .01), respectively. This inhibition was not agonist specific but occurred with multiple agonists including FMLP, PMA, A23187, and Zymosan-activated serum (ZAS). Last, cyclosporin and verapamil did not modulate the anthracycline effects of PMN superoxide generation. This study suggests that two of the newest anthracyclines, epirubicin and idarubicin, inhibit more PMN superoxide radical formation compared to their parent compounds. This reduction in oxyradical formation may account in part for their difference in anthracyline cellular cytotoxic activity.
Immunologic Consequences of Taurine Deficiency in Cats
Authors: Schuller-Levis Georgia , Mehta Pankaj D , Rudelli Raul , Sturman John 
Published: January 2018

Abstract
Our results show that a lack of taurine in the diet of cats results in a significant leukopenia, a shift in the percentage of polymorphonuclear and mononuclear leukocytes, an increase in the absolute count of mononuclear leukocytes, and a change in the sedimentation characteristics of white cells. Functional studies of polymorphonuclear cells isolated from cats fed taurine-free diets show a significant decrease in the respiratory burst as measured by chemiluminescence as well as a decrease in phagocytosis of Staphylococcus epidermis compared to cats fed the same diet containing taurine. In addition, serum gamma globulin in cats fed taurine-free diets was significantly increased compared to taurine-supplemented cats, indicating that other immune cells may be affected by taurine deficiency. Histological examination of lymph nodes and spleen revealed regression of follicular centers with depletion of reticular cells, mature and immature lymphocytes (B cell areas), as well as mild extravascular hemolysis. These results indicate that there are profound immunologic consequences in cats with prolonged taurine deficiency.
Purification of Tryptase From a Human Mast Cell Line
Authors: Butterfield Joseph H , Weiler Deborah A , Hunt Loren W , Wynn Susan R , Roche Patrick C 
Published: January 2018

Abstract
The neutral protease tryptase has been isolated from a human mast cell line, HMC-1. The HMC-1 line was established from the peripheral blood of a patient with mast cell leukemia and maintained as continuously proliferating clones in vitro and as solid mast cell tumors in nude mice. HMC-1-derived tryptase was purified by sequential chromatography on Dowex 1, DEAE 5 PW, and heparin-agarose. Purified tryptase has an apparent molecular weight of 150,000, as determined by molecular sieve HPLC, but migrates as a doublet of bands of 32/35,000 on SDS-PAGE gels. Maximal enzymatic activity was observed at pH 8.5. Cleavage of tosyl-L-arginine methyl ester by purified tryptase was inhibited by dansyl-L-glutamyl-glycyl-L-arginine chloromethyl ketone 2 HCI, HgCI2, tosyl-L-lysine chloromethyl ketone, leupeptin, and PMSF but not by benzamidine, aprotinin, tosyl-L-phenylalanine chloromethyl ketone, soybean trypsin inhibitor, human plasma, ovomucoid inhibitor, or lima bean trypsin inhibitor. Microsequencing of purified tryptase yielded an amino terminal sequence that was identical to that previously reported for human pituitary-derived tryptase.
Flow Cytometric Analysis of Respiratory Burst Activity in Phagocytes With Hydroethidine and 2′,7′-Dichlorofluorescin
Authors: Rothe Gregor , Valet Günter 
Published: January 2018

Abstract
Hydroethidine (HE) and 2′,7′-dichlorofluorescin (DCFH) were used for the flow cytometric measurement of reactive oxygen metabolites in leukocytes. Hydroethidine and DCFH were both rapidly oxidized in a cell-free cuvette assay to ethidium bromide (EB) and 2′,7′-dichlorofluorescein (DCF) by H2O2 and peroxidase, but not by H2O2 alone, while only HE was oxidized by KO2, a source of O-2. Quiescent lymphocytes, monocytes, and neutrophils spontaneously oxidized HE to EB, while DCFH was only oxidized to a low degree. Neutrophils increased 6.9-fold in EB red fluorescence and 12.5-fold in DCF green fluorescence during the respiratory burst induced by phorbol 12-myristate 13-acetate or 6.1-fold and 4.7-fold, respectively, during the respiratory burst induced by Escherichia coll bacteria. The HE or DCFH oxidation during the respiratory burst, unlike the spontaneous HE oxidation, was not inhibitable by 10 mM NaN. indicating a non-mitochondrial source of cellular oxidants during the respiratory burst such as NADPH oxidase, which produces O-2. The oxidation of DCFH, but not of HE, was decreased in stimulated neutrophils, which were simultaneously loaded with HE and DCFH. Intracellular DCFH oxidation induced by incubation of resting neutrophils with extracellular H2O2 was not influenced by the presence of HE. This indicates that HE is oxidized at an earlier step in the reactive oxygen metabolism of neutrophils than DCFH, i.e., by early oxygen metabolites like O2-, while DCFH is oxidized in part by H2O2 and phagosomal peroxidases. The differential oxidation of HE and DCFH during simultaneous cellular staining permits the analysis of up to three functionally different neutrophil populations in septic patients. This is of interest for the determination of disease-related alterations of oxygen metabolism in quiescent and stimulated leukocytes.