bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling pathways mediated by the mitogen-activated protein (MAP) kinase kinase/MAP kinase cascade
Authors: Matsuda Satoshi , Gotoh Yukiko , Nishida Eisuke 
Published: January 2018

Abstract
Mitogen-activated protein (MAP) kinase and its direct activator, MAP kinase kinase (MAPKK), comprise the MAPKK/MAP kinase cascade, which may play a pivotal role in a variety of intracellular signal transduction pathways from yeast to human. Vertebrate MAPKK, a dual-specificity kinase, is activated by serine phosphorylation catalyzed by upstream serine/threonine kinases, MAPKK kinases (MAPKK-Ks). MAPKK is, on the other hand, threonine phosphorylated by MAP kinase, although a physiological role of this MAP kinase–mediated phosphorylation of MAPKK is unknown. Biochemical fractionation of extracts from Xenopus mature oocytes revealed two major and one minor peaks for the MAPKK-K activity. One of the major peaks contained a proto-oncogene product c-Mos, while the other peaks did not. These observations, together with a recent finding that several MAPKK-Ks such as Raf-1 and MEKK may function within a cell, suggest a diversity of MAPKK-Ks. A variety of extracellular signals converge at the MAPKK/MAP kinase cascade through different MAPKK-Ks and elicit a wide spectrum of cellular responses. Therefore, mechanisms that control activation of the MAP kinase cascade temporally and spatially may be important for specification of cellular responses. J. Leukoc. Biol. 56: 548-553; 1994.
Differential effects of temperature on macrophages of ectothermic vertebrates
Authors: Pxytycz Barbara , Józkowicz Alicja 
Published: January 2018

Abstract
The role of macrophages in vertebrate defense reactions is especially important at low temperatures, which commonly affect representatives of ectothermic species. The aim of this work was to compare the effects of in vivo thermal acclimation and in vitro assay temperatures on peritoneal macrophages (PMs) from fish (carp and goldfish) and amphibians (salamanders and toads). The substratum adherence of PMs was undisturbed over the wide range of temperatures experienced by animals in nature. Dehydrogenases and endocytosis were sensitive to temperature fluctuations in a species-specific manner, more or less dependent on the previous thermal history of animals. The MTT reduction, inhibited by low assay temperatures, was slightly improved in PMs from cold-acclimated amphibians but not fishes. Endocytosis by the amphibian PMs, very efficient over the wide range of assay temperatures, was additionally improved by previous in vivo cold exposure. Contrasting effects of thermal acclimation were most evident in the case of endocytic properties of fish PMs; endocytosis by PMs from cold-acclimated fishes was extraordinarily efficient at a temperature just above zero, which almost completely inhibited cells from fishes adapted to warmth. J. Leukoc. Biol. 56: 729–731; 1994.
The role of IL-4, IL-10, and TNF-α in the immune suppression induced by ultraviolet radiation
Authors: Rivas Jorge M , Ullrich Stephen E 
Published: January 2018

Abstract
Cytokines produced by keratinocytes play an essential role in the induction of immune suppression following ultraviolet (UV) exposure. Using antibodies specific for either interleukin-10 (IL-10) or tumor necrosis factor α (TNF-α), we present evidence indicating that IL-10 suppresses delayed-type hypersensitivity (DTH) but not contact hypersensitivity (CHS), whereas TNF-α suppresses CHS but not DTH following UV exposure. UV exposure also activates antigen-specific suppressor T cells. To determine whether the antigen-specific CD4+ T cells that transfer suppression in this system mediate their suppressive effect by releasing IL-4 or IL-10, we transferred UV Ts into normal mice that were then injected with either anti-IL-4 or anti-IL-10 antibody. Both anti- IL-4 and anti-IL-10 blocked the ability of UV Ts cells to suppress DTH in the recipient animals. When UV Ts that suppress CHS were transferred into normal recipients, however, neither antibody was able to block the UV Ts activity. These findings suggest that UV Ts suppress DTH by secreting IL-4 and IL-10 and appear to act like Th2 cells. Because anti-IL-4 and anti-IL-10 did not block the activity of the UV Ts that regulate contact hypersensitivity, their effects appear to be mediated by a different mechanism. J. Leukoc. Biol. 56: 769–775; 1994.
Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal corticosteroids
Authors: Suzuki Hidekazu , Zweifach Benjamin W , Forrest Michael J , Schmid-Schönbein Geert W 
Published: January 2018

Abstract
Leukocyte adhesion is a key factor in the pathogenesis of organ injury following a variety of stimuli. In this study we have addressed the role of leukocyte adhesion in hypertensives as a risk factor for organ injury. In the spontaneously hypertensive rat (SHR), the number of circulating leukocytes and their level of activation are significantly increased compared with its normotensive control, the Wistar-Kyoto rat (WKY). We have demonstrated that elevated levels of glucocorticoid in SHR suppress P-selectin–mediated leukocyte-endothelial interaction in the microcirculation. It is possible that the disturbance in leukocyte-endothelial interactions may result in an elevated number of leukocytes in the circulation. The aim of the present study was to investigate the contribution of the adrenal glands to the disturbance in leukocyte behavior in SHR by subjecting the animals to bilateral adrenalectomy and investigating the effect of hydrocortisone. In addition, we have studied by immuno-histochemistry the expression of the endothelial adhesion molecule, P-selectin, in response to histamine in the mesenteric venules of normal and adrenalectomized SHR and WKY. The elevated blood pressure, above-normal leukocyte counts, and elevated number of activated neutrophils (nitroblue tetrazolium test) in SHR were blunted after adrenalectomy. The blunted histamine-induced leukocyte-endothelial interaction in the mesenteric venules of SHR was restored after adrenalectomy. Treatment with hydrocortisone significantly attenuated the elevated leukocyte adhesion in the adrenalectomized SHR as well as in WKY. The suppressed P-selectin expression in SHR mesentery was restored after adrenalectomy. In conclusion, the subnormal leukocyte-endothelial interaction in response to an inflammatory stimulation in SHR is abolished after adrenalectomy, suggesting a relationship between the altered leukocyte adhesiveness and the adrenal corticosteroids in hypertensives. J. Leukoc. Biol. 57: 20–26; 1995.
Characterization of eosinophil homotypic aggregation
Authors: Teixeira Mauro M , Williams Timothy J , Au Bo-Ting , Hellewell Paul G , Rossi Adriano G 
Published: January 2018

Abstract
Guinea pig peritoneal eosinophils stimulated by platelet-activating factor (PAF), leukotriene B4 (LTB4), and human recombinant C5a (C5a) undergo a rapid concentration-dependent and partially reversible homotypic aggregation as assessed by changes in light transmission. The phorbol ester phorbol myristate acetate similarly induces a concentration-dependent aggregation, which is, however, slower in onset, takes longer to reach maximal aggregation, and is irreversible. In addition, we confirmed, using light microscopy, that these agonist-induced changes in light transmission do indeed represent true homotypic aggregation. We further characterized the aggregation response and showed that there is homologous but little heterologous desensitization when PAF and LTB4 are used as stimuli. A requirement for both Ca2+ and Mg2+ for full manifestation of agonist-induced aggregation was observed. LTB4- and PAF-induced superoxide anion generation is enhanced by the diacylglycerol kinase inhibitor R59022, whereas aggregation induced by LTB4, but not PAF, is augmented. Lastly, we show that eosinophil aggregation is partially dependent on the adhesion glycoprotein CD18. In summary, therefore, we believe that eosinophil aggregation provides a useful and reliable measure of eosinophil activation. J. Leukoc. Biol. 57: 226–234; 1995.
Transforming growth factor β modulates C3 and factor B biosynthesis and complement receptor 3 expression in cultured human monocytes
Authors: Høgåsen Anne Kirsti Myrvang , Hestdal Kjetil , Høgåsen Kolbjørn , Abrahamsen Tore G 
Published: January 2018

Abstract
Complement biosynthesis in monocytes is stimulated by different pathogens and modulated by a variety of cytokines, but little is known about the possible effect of transforming growth factor β (TGF-β) on this monocyte function. We therefore studied the effect of TGF-βl and TGF-β2 on constitutive, lipopolysaccharide (LPS)- and Candida albicans-induced monocyte biosynthesis of complement components C3 and factor B. Under all three conditions, both forms of TGF-β (20 ng/ml) induced a two- to fourfold increase in C3 concentration in monocyte supernatants harvested after 2 or 5 days of cell culture, an effect that was abrogated by cycloheximide. In contrast, constitutive and pathogen-induced production of factor B was suppressed by TGF-β. The effects of TGF-β on complement production were neutralized by a monoclonal anti-TGF-β antibody. Moreover, TGF-β suppressed the pathogen-induced release of granulocyte-macrophage colony-stimulating factor and down-regulated the expression of complement receptor 3 (CD11b/CD18), while the expression of CD11a/CD18, a related β 2 integrin, was unaffected. These novel effects of TGF-β emphasize the immunomodulatory significance of this cytokine. J. Leukoc. Biol. 57: 287–296; 1995.
Activation of casein kinase II in ML-1 human myeloblastic leukemia cells requires IGF-1 and transferrin
Authors: Wang L G , Liu X M , Wikiel H , Bloch A 
Published: January 2018

Abstract
Casein kinase II (CK II), a key enzyme involved in the regulation of cell growth, has been variously reported to be activated by diverse mitogens, including insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). Activation of the enzyme is generally carried out in the presence of serum, and we examined the question whether serum components participate in the activation process. We demonstrated previously that ML-1 cells require IGF-1 plus transferrin (TF) for growth and transforming growth factor β or tumor necrosis factor α plus TF for differentiation. We now found that CK II is activated only when the cells are exposed to both IGF-1 and TF or when TF is replaced in this combination with relatively high levels of iron salts. Induction of differentiation with TGF-β and TF did not result in CK II activation. These results show that CK II activation in ML-1 cells requires the application of both components of the growth signal, IGF-1 and TF, demonstrating that the growth factor alone is incapable of enhancing the activity of the enzyme. J. Leukoc. Biol. 57: 332–334; 1995.
75- but not 55-kDa tumor necrosis factor receptor is active in the homotypic aggregation and proliferation of human lymphokine-activated T killer (T-LAK) cells in vitro
Authors: Abe Yasuhito , Yamauchi Kuniyoshi , Kimura Shigeru 
Published: January 2018

Abstract
Lymphotoxin (LT) and tumor necrosis factor (TNF) play important roles in the maturation and growth of human lymphokine-activated T killer (T-LAK) cells in vitro. The role of 55- and 75-kDa TNF receptor (TNF-R) in the aggregation and proliferation of T-LAK cells was investigated using agonistic anti-TNF-R rabbit polyclonal antibodies. Human peripheral blood T cells and T-LAK cells predominantly express 75-kDa TNF-R. The proliferation of T-LAK cells during the generation phase is supported by innate LT and TNF. In this phase, the proliferation was upregulated by anti–75- but not 55-kDa TNF-R antibody. Homotypic aggregation of T-LAK cells was induced by LT, TNF, and anti–75- but not by anti–55-kDa TNF-R antibody. The increase of homotypic aggregation was accompanied by up-regulation of intercellular adhesion molecule 1 but not lymphocyte function–associated antigen 1 expression on cells and by an elevation of membrane fluidity, both of which were up-regulated by anti–75- but not 55-kDa TNF-R antibody. Interestingly, LT and TNF suppressed the proliferation of mature T-LAK cells. Anti–75- but not 55-kDa TNF-R antibody suppressed the proliferation, mimicking LT and TNF. These findings indicated that 75- but not 55-kDa TNF-R is biologically active in the modulation of aggregation and proliferation of human T-LAK cells in vitro. J. Leukoc. Biol. 57: 462–468; 1995.
Synergism between interferon-γ and cytokines or lipopolysaccharide in the activation of the HIV-LTR in macrophages
Authors: Warfel Alwin H , Thorbecke G Jeanette , Belsito Donald V 
Published: January 2018

Abstract
Macrophages (mfs) obtained from transgenic mice carrying the HIV long terminal repeat-chloramphenicol acetyl transferase (LTR-CAT) sequence were used to study the influence of various biologic response modifiers (BRMs) on the activation of LTR-directed CAT expression. It was found that LPS or IL-6 alone induced moderate levels of CAT expression, whereas IFN-γ or TNF-α had no significant effect. Co-exposure of mφs to IFN-γ and either LPS, IL-6, or TNF-α led to significant synergistic increases in CAT levels. Levels were also synergistically augmented when mφs were exposed first to IFN-γ (priming), washed, and then exposed to either LPS, IL-6, or TNF-α. Although IL-6 was synergistic with subsequently added IFN-γ, the reverse sequence of addition was more effective. LPS and TNF-α were inactive when added before IFN-γ. Initial priming signals were rapid as exposure for 3 h to IFN-γ was sufficient to prepare the cells for subsequent activation by other BRMs. These results suggest that the duration of latency and progression of HIV infections may be greatly influenced by events such as intercurrent infections that cause IFN-γ production, thereby priming mfs to respond to other cytokines that have been reported to be constitutively elevated during the course of infection with HIV (e.g., IL-6 and/or TNF-α). J. Leukoc. Biol. 57: 469–476; 1995.
Identification of macrophage activation associated proteins by two-dimensional gel electrophoresis and microsequencing
Authors: Walsh B J , Gooley A A , Williams K L , Breit S N 
Published: January 2018

Abstract
To understand activation in monocytes and macrophages we have studied changes in protein synthesis using the human monocytoid U937 cell line and twodimensional polyacrylamide gel electrophoresis (2D PAGE) and protein sequencing. U937 cells that had been metabolically labeled during treatment with PMA, LPS, or IFN-γ showed appreciable increases or decreases in synthesis of 14 proteins when analyzed by 2D PAGE. Although some 20 proteins are reported to be affected by these agents in U937 cells, none of them correspond with the 14 proteins studied here. Of the 14 observed changes, four spots (p41/65, p35/65, p26/44, p20/53) were up-regulated by PMA only, one (p16/44) by LPS only, five spots (p29/47, p26/45, p26/48, p12/47, p10/45) by both LPS and PMA, and, finally, one (p29/45) by all three agents. Two spots (p20/59 and p20/61) were down-regulated by IFN-γ and one of these spots (p20/59) was up-regulated by LPS. Only one spot (p20/48) was up-regulated by IFN-γ. Eleven spots with matching mobilities (both Mr and pI) to those identified in U937 were observed on 2D PAGE gels from human culture derived macrophages. Ten spots from U937 were sequenced by Edman degradation. Two were could not identified from information contained in the available DNA and protein databases and thus represent novel proteins, whereas a further six of the proteins were N-terminally blocked. The remaining two (29/47 and 12/47, respectively) were identified from existing protein databases as translationally controlled tumor protein (TCTP) and cytokeratin. This is the first report of the presence of TCTP in hemopoietic cells and its modulation by PMA or LPS in any cell type. We believe that 2D PAGE and sequencing is a powerful approach for identifying key proteins in macrophage cellular activation. J. Leukoc. Biol. 57: 507–512; 1995.
Monoclonal antibody EG2 reactivity: the need for clarification
Authors: Rosenberg Helene F , Lee Tiffany H 
Published: January 2018

Abstract
Authors’ reply: We are puzzled by the reaction of Jahnsen and Brandtzaeg to our paper [1], In this work, we determined that the capacity of mAb EG2’s to react with both eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) was directly dependent on the glycosylation state of these granule proteins. We showed that mAb EG1 detected all glycosylated forms of ECP, whereas the mAb EG2 detected only the least glycosylated (and deglycosylated) forms of both ECP and EDN. We attempted to reconcile these purely biochemical findings with the prevailing understanding of these antibodies—indeed, the only published data at the time this work went to press—which was that the mAb EG1 detected both resting and activated eosinophils, while EG2-reactivity was an indicator of eosinophil activation and secretion [2]. Our experiments were not designed to determine the validity of this claim; in fact, our conclusions included the possibility that the EG2-reactive forms of ECP and EDN existed within the resting eosinophil granule, in a location or conformation rendering them inaccessible to the antibody under standard fixation conditions (1).
NFATp, a cyclosporin-sensitive transcription factor implicated in cytokine gene induction
Authors: Rao Anjana 
Published: January 2018

Abstract
The transcription factor NFATp (nuclear factor of activated T cells, preexisting) is likely to regulate the cyclosporin-sensitive transcription of cytokine genes and other activation-associated genes during the immune response. NFATp is the first identified member of a new family of transcription factors, whose DNA binding do mains show a weak sequence similarity to those of the Rel (NF-xB) family of proteins. NFATp is expressed in several types of immune cells as a cytosolic protein that translo cates to the nucleus following activation. The nuclear translocation is regulated by calcium and calcineurin and inhibited by cyclosporin A and FK506. In the nucleus, NFATp cooperates with Fos-Jun dimers and possibly with other transcription factors at composite elements in the regulatory regions of cytokine genes. The potential roles of NFATp and a related family member, NFATc, in cytokine gene transcription are discussed. J. Leukoc. Biol. 57: 536–542; 1995.
Functional significance of two cytolytic pathways of cytotoxic T lymphocytes
Authors: Podack Eckhard R 
Published: January 2018

Abstract
Cytotoxic lymphocytes are equipped with several effector molecules mediating cytotoxicity. Two pathways have been molecularly defined and functionally characterized through the analysis of deficiency states. It is evident from these results that lysis by granule exocytosis serves primarily to eliminate exogenous and en dogenous hazards such as virally infected and trans formed cells. In contrast, lysis by induced suicide in the fas pathway is used to maintain homeostasis of rapidly expanding and contracting cell populations including T cells. J. Leukoc. Biol. 57: 548–552; 1995.
Extracellular matrix proteins and leukocyte function
Authors: Pakianathan Deepika R 
Published: January 2018

Abstract
Extracellular matrix (ECM) proteins profoundly affect physiological functioning at the cellular level. Cell growth and differentiation, as well as cell shape and migration via the cytoskeleton, are all affected by ECM proteins. Leukocyte interactions with matrices have recently become an exciting field of research because a number of different leukocyte functions are significantly affected by their binding to ECM proteins. This may be especially important in inflammatory responses where leukocytes are primed for inflammatory mediator and cytokine production by binding to ECM proteins during extravasation. Because activated leukocytes produce potentially damaging substances, the progress of an inflammatory response can be profoundly affected by the ECM proteins encountered by leukocytes during their migration from within the peripheral circulation to sites of inflammation. This review summarizes recent publications describing components of the ECM that influence leukocyte function, the receptors involved in leukocyte binding to ECM proteins, and focuses on the effects of ECM proteins on the production of inflammatory mediators and cytokines by human peripheral blood leukocytes. J. Leukoc. Biol. 57: 699–702; 1995.
Induction of macrophage suppressor activity by fibrosarcoma-derived transforming growth factor-β1: contrasting effects on resting and activated macrophages
Authors: Alieva David G , Walker Thomas M , Elgert Klaus D 
Published: January 2018

Abstract
Tumor-derived transforming growth factor-β1 (TGF-β1) suppresses several immune responses. Because tumor growth induces macrophage (mφ) suppressor activity, we determined whether murine fibrosarcoma-derived TGF-β1 contributed to mφ-mediated suppression of autoantigen- and alloantigen-stimulated T cell proliferation. The murine fibrosarcoma Meth-KDE cell line constitutively produced TGF-β1. Meth-KDE tumor-bearing host (TBH) syngeneic splenic mφs suppressed autoantigen- and alloantigen-stimulated normal host (NH) CD4+ T cell proliferation. Pretreatment with Meth-KDE supernatants induced NH mφs to suppress T cell proliferation as much as TBH mφs. Anti-TGF-β1 antibody treatment reversed Meth-KDE-induced NH mφ-mediated suppression. Recombinant TGF-β1-induced mφ-mediated suppression was not blocked during inhibition of prostaglandin E2 (PGE2), nitric oxide (NO), or TGF-β1 production. However, Meth-KDE-induced mφ-mediated suppression was partly reduced when PGE2 production was inhibited. Pretreatment with tumor cell-derived TGF-β1, but not recombinant TGF-β1, increased activated mφ PGE2 production. These results show that additional tumor-derived molecules aid in TGF-β1-enhanced PGE2 production. Also, TGF-β1 alone up-regulates mφ synthesis of suppressor molecules that are different from PGE2, NO, and TGF-β1. Although TGF-β1 has direct suppressor activity on lymphocytes, these results show that release of tumor cell TGF-β1 also induces mφ suppressor activity. J. Leukoc. Biol. 57: 919–928; 1995.
Interferon-α and interferon-γ down-regulate the production of interleukin-8 and ENA-78 in human monocytes
Authors: Schnyder-Candrian Silvia , Strieter Robert M , Kunkel Steven L , Walz Alfred 
Published: January 2018

Abstract
The two chemotactic cytokines interleukin-8 (IL-8) and epithelial neutrophil activating protein 78 (ENA-78) were recently shown to be potent chemoattractants and activators of neutrophil function and to be present in certain inflammatory diseases. We have studied the effects of recombinant and natural interferon-α (IFN-α) and of recombinant interferon gamma (rIFN-γ) on the production of EL-8 and ENA-78 in lipopolysaccharide- and interleukin-1–stimulated human monocytes. Both types of interferons showed a strong, concentration-dependent inhibition of neutrophil-stimulating bioactivity. Similarly, the secretion of IL-8 and ENA-78 was also inhibited by up to 73%. Northern blot experiments demonstrated that IFN-α decreases the steady-state levels of IL-8 and ENA-78 mRNA in monocytes, suggesting that IFN-α as well as IFN-γ may control the expression of neutrophil chemotactic cytokines at the mRNA level. J. Leukoc. Biol. 57: 929–935; 1995.