bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secreted glucocorticoids regulate leukocyte-endothelial interactions in inflammation. A direct vital microscopic study
Authors: Farsky Sandra P , Sannomiya Paulina , Garcia-Leme J 
Published: January 2018

Abstract
Leukocytes come into intimate contact with the venular endothelium as they extravasate from blood to the interstitium during inflammation. In exteriorized tissues, the number of leukocytes rolling along the vessel wall was markedly increased in adrenalectomized and metyrapone-treated animals, relative to sham-operated and normal animals. During the development of an acute, local inflammatory response, rollers were numerically decreased and a stronger adhesion of the cells to the endothelium, with a concomitant migration into tissues, was observed. Adhesion and migration were much more marked in adrenalectomized and metyrapone-treated animals than in controls, suggesting that secreted glucocorticoids exert a suppressive effect on leukocyte-endothelial interactions. The increased number of rolling leukocytes in adrenalectomized and metyrapone-treated animals apparently resulted in more cells available to migrate into inflamed tissues. The effect appears to involve receptor occupancy and induction of gene expression because normal animals receiving the steroid antagonist RU 38 486, actinomycin D, or cydoheximide behaved as adrenalectomized or metyrapone-treated animals. Administration to adrenalectomized animals of a monoclonal antibody to the membrane glycoprotein complex GD18 did not affect the number of rolling cells, but dramatically reduced the number of adherent or migrated leukocytes. It is suggested that secreted glucocorticoids, in addition to an effect on rolling behavior of circulating leukocytes, might also modulate the activity of the glycoprotein complex CD18 on white blood cells. The ultimate consequence is a restrictive effect on cell emigration in inflammation. J. Leukoc. Biol. 57: 379–386; 1995.
The role of the innate immune response in Th1 cell development following Leishmania major infection
Authors: Scharton-Kersten Tanya , Scott Phillip 
Published: January 2018

Abstract
Infection of mice with the protozoan parasite Leishmania major is an established model with which to study the in vivo development of CD4+ Th cell subsets. Interferon-γ (IFN-γ), produced by natural killer (NK) cells (AsGM1+, CD4-, CD8-, CD3-), regulates CD4+ T cell subset development and early resistance to L. major. Rapid Th1 cell development and resistance to infection occur in mice that develop an NK cell response early after infection (C3H and immunized BALB/c mice), whereas mice that lack an early NK cell response demonstrate delayed Thl cell development and enhanced early disease (C57BL/6) or lack detectable Thl cell development al together and develop a progressive, fatal infection (BALB/c). Analysis of the requirements for NK cell acti vation in C3H mice revealed that the NK cell response is both interleukin-2 (IL-2) and IL-12 dependent. Although delayed IL-12 production in C57BL/6 mice precludes NK cell activation, the eventual development of a Thl re sponse appears to be IL-12 dependent. In contrast, con comitant production of inhibitory factors (IL-4, IL-10, and transforming growth factor β) with IL-12 and IL-2 prevents NK cell activation in BALB/c mice. Together, these observations support a paradigm of in vivo Th1 cell development that involves IL-12-depcndcnt stimulation of IFN-γ production by NK cells. J. Lcukoc. Biol. 57: 515–522; 1995.
A direct signaling pathway through tyrosine kinase activation of SH2 domain-containing transcription factors
Authors: Fu Xin-Yuan 
Published: January 2018

Abstract
Studies on the mechanism of interferoninduced gene expression revealed a direct signaling path way from ccl1 surface receptors to transcription factors. In this pathway, signal transduction is mediated by a new class of transcription factor STAT (signal transducer and activator of transcription). We have shown that STAT fac tors contain Src homology region 2 and 3 domains and arc phosporylated and activated in the cytoplasm by rcccptor associated tyrosine kinases. The activated tran scription factors then translocate to the nucleus, joined by a nuclcar DNA binding factor, to form an active tran scriptional complex. Recent studies have shown that this direct signaling pathway is the key to control of gene ex pression induced by many cytokines and growth factors. J. Leukoc. BioL 57: 529–535; 1995.
Pathways for the processing and presentation of antigens to T cells
Authors: Monaco John J 
Published: January 2018

Abstract
Two pathways exist within vertebrate cells to generate peptides for recognition by T cells. The “en dogenous” pathway provides peptides to MHC class I molecules for presentation to CD8+ T cells. These pep tides are derived from proteins synthesized or residing in the cytoplasm or nucleus, and involves proteasomes and the ubiquitin pathway of protein degradation, as well as a specific peptide transporter (TAP) that allows these pep tides access to the lumen of the endoplasmic reticulum. The exogenous pathway provides peptides to MHC class II molecules for presentation to CD4+ T cells. These pep tides are derived from extracellular antigens taken up by endocytosis and degraded in the endosomal/lysosomal pathway. Peptide loading of MHC class II molecules re quires the presence of a molecule (H-2M in mouse, HLA-DM in humans) that is structurally related to MHC class II molecules, but the mechanistic basis of this require ment is unknown. The class II region of the MHC con tains a cluster of genes encoding proteins involved in an tigen processing, including genes for two proteasome subunits (LMP2 and LMP7), the peptide transporter hetcrodimer (TAPI and TAP2), and the H-2M/HLA-DM molecule (Ma and Mb, or DMA and DMB). J. Lcukoc. Biol. 57: 543–547; 1995.
Effects of granulocyte colony-stimulating factor and interferon-γ on antifungal activity of human polymorphonuclear neutrophils against pseudohyphae of different medically important Candida species
Authors: Roilides Emmanuel , Holmes Andrew , Blake Cassann , Pizzo Philip A , Walsh Thomas J 
Published: January 2018

Abstract
Polymorphonuclear neutrophils (PMNs) are the major host defense against pseudohyphae, the inva sive form of Candida species. We studied the effects of granulocyte colony-stimulating factor (G-CSF) and interfcron-γ (IFN-γ) on the PMN-induced damage of pseudohyphae of Candida albicans, Candida tropicalis, and Candida parapsilosis in vitro by using two antifungal assays: a modified limiting dilution assay and a colorimet ric metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tctraznlium bromide assay. PMNs from healthy volunteers were ineubated with either G-CSF (100-10,000 U/ml) or IFN-γ (10-5000 U/ml) or buffer at 37° C for 90 min and their capacity to damage nonopsonized pseudohyphae was then measured. C. tropicalis appeared to be the most susceptible species, whereas C. parapsilosis showed the highest rate of rcsistancc to PMN damage. G-CSF (500–10T000 U/ml) and IFN-γ (100-1000 U/ml) enhanced the antifungal activity of PMNs against C. albicans pseudo hyphae (P &lt; .01 and P &lt; .05). Among the others, G-CSF enhanced PMN-induccd damage of C. parapsilosis at concentrations 500–10,000 U/ml (P &lt; .05), whereas it enhanced damage of C, tropicalis only at 10,000 U/ml (P &lt; .01), IFN-γ (100–1000 U/ml) primed PMNs also caused augmented damage of C. parapsilosis (P &lt; .05) but not of C, tropicalis at the same concentrations. Species-dependent differences exist in the responses of PMNs to Candida pseudohyphae and G-CSF as well as IFN-γ are important immunomodulators of phagocytic host defenses against them Leukoc. Biol. 57: 651–656; 1995.
Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages
Authors: Lewis C E , Leek R , Harris A , McGee J O’D 
Published: January 2018

Abstract
Studies over the past 20 years have established that the development of new capillaries from an existing vascular network (a process called angiogenesis) is an essential component of tumor growth. Malignant tumors do not grow beyond 2–3 mm3 in size unless they stimulate the formation of new blood vessels and thus provide a route for the increased inflow of nutrients and oxygen and outflow of waste products. Tumor angiogenesis also provides an essential exit route for metastasizing tumor cells from the tumor to the bloodstream. Indeed, extensive neovascularization is a poor prognostic factor in several forms of human cancer. Angiogenesis is a complex, multistep process driven by many local signals within the tumor. This involves the degradation of the extracellular matrix around a local venule after the release of collagenases and proteases, the proliferation and migration of capillary endothelial cells, and their differentiation into functioning capillaries. Cytokines produced by various cell types present within the microenvironment of solid tumors form a complex, dynamic network in which they have multiple effects on tumor progression. Herein we review our work on the presence, and possible regulatory influence on tumor angiogenesis, of a number of these cytokines within invasive breast carcinomas. We have combined immunocyto-chemistry with a single cell cytokine release assay called the reverse hemolytic plaque assay to investigate the cellular sources of the key angiogenic cytokines, vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor-α. Tumor-associated macrophages in the stromal compartment of these tumors and/or malignant epithelial cells were seen to be a major producer cell for these cytokines, whereas tumor necrosis factor-α receptors were expressed by leukocytes, malignant cells, and endothelial cells in tumor blood vessels. J. Leukoc. Biol 57: 747–751; 1995.
Cell line cross-contamination of U-397
Authors: Reid Yvonne A , O’Neill Kathleen , Chen T R , Dorotinsky Catherine , McGuire Linda , Macy Marv , McCuntock Patrick , Hay Robert 
Published: January 2018

Abstract
To the Editor: The human histiocytic lymphoma cell line, U-937, established by S. Sundström and K. Nilsson in 1974 (1), was deposited at American Type Culture Collection (ATCC) in 1981 by H. Koren, Duke University Medical Center, Durham, N.C. A starter culture obtained from the depositor was propagated through one passage to generate a “token” freeze (F-2704). Progenies from ampules of this cryopreserved material were expanded to produce the “seed” stock (F-2717) and initial distribution stocks. The seed stock is retained to generate new distribution stocks that are provided to scientific investigators. Cultures derived from token, seed, and distribution stocks were tested for microbial and mycoplasma contamination. The cell line species of origin was confirmed by routine isoenzymology and karyology.
Relationship of phospholipase C- and phospholipase D-mediated phospholipid remodeling pathways to respiratory burst activation in human neutrophils stimulated by Candida albicans hyphae
Authors: Meshulam Tova , Billah M Motasim , Eckel Stephen , Griendling Kathy K , Diamond Richard D 
Published: January 2018

Abstract
Neutrophil (PMN) oxidant release, a key component of defenses against disseminated candidiasis, was preceded by oxidant generation after stimulation by Candida albicans hyphae. Opsonized or unopsonized hyphae triggered phospholipase D (PLD) activation within 5 or 30 s, respectively, forming 1-O-alkyl-phosphatidic acid (alkyl-PA) or 1-O-alkyl-phosphatidyl-ethanol in the presence of ethanol. Ethanol, which competitively lowers phosphatidic acid (PA) production, caused dose-dependent inhibition of superoxide (O2-) generation after hyphal stimulation but altered neither baseline-unstimulated O2- production nor responses to phorbol myristate acetate. PA rises evoked by unopsonized hyphae began 2 min before significant O2- release, also preceding both phospholipase C activation and cytosolic Ca2+ rises. Diacylglycerol (DAG) rose in two distinct phases after stimulation by opsonized or unopsonized hyphae, peaking briefly after 60 or 120 s, respectively, followed by prolonged secondary rises. Initial DAG rises preceded inositol triphosphate elevations evoked by unopsonized hyphae. Though PA rose before DAG, no dephosphorylation of PA to form 1-O-alkyl-DAG was noted. Propranalol, which increases PA accumulation by inhibiting PA phosphohydrolase, lowered PMN O2- responses to hyphae. Early DAG rises temporally overlapped respiratory burst initiation but PMN responses to hyphae were unchanged by a DAG kinase inhibitor, R59022, which blocks phosphorylation of DAG to PA and enhances DAG accumulation. Thus, neither PA nor DAG accumulation individually accounted for triggering PMN O2- responses to hyphae. PLD activation and PA production may facilitate PMN fungicidal responses to hyphae but play an indirect role in initiating the respiratory burst. J. Leukoc. Biol. 57: 842–850; 1995.
Human eosinophils in culture undergo a striking and rapid shrinkage during apoptosis. Role of K+ channels
Authors: Beauvais Francis , Michel Laurence , Dubertret Louis 
Published: January 2018

Abstract
In the absence of appropriate stimulus, eosinophils in vitro rapidly exhibit the features of apoptotic cells (nuclear pycnosis, cell shrinkage, DNA fragmentation). By using electronic cell sizing, we precisely measured the volume distribution of human eosinophils during apoptosis. We observed that apoptosis of eosinophils was accompanied by a marked cell volume decrease (approximately 60%). Moreover, analysis of the volume distribution in different experimental conditions (kinetics of apoptosis, inhibition of apoptosis by cytokines) revealed that the cell shrinkage, once triggered, was a fast process in which the intermediate states between normal and shrunken volume had a short half-life. As a model of apoptosis, the eosinophil model allowed us to test the hypothesis that apoptotic cell shrinkage was linked to osmotic changes due to leakage of internal ions. Indeed, in the presence of K+ channel blockers, the shrinkage was inhibited in a dose-dependent manner. In conclusion, our results suggest that eosinophil shrinkage during apoptosis is a striking and rapid phenomenon and osmotic changes due to K+ efflux could be responsible, at least in part, of the volume decrease. J. Leukoc. Biol. 57: 851–855; 1995.
Lipopolysaccharide-inactivating activity of neutrophils is due to lactoferrin
Authors: Wang Demin , Pabst Karen M , Aida Yoshitomi , Pabst Michael J 
Published: January 2018

Abstract
Neutrophils can inactivate lipopolysaccharide (LPS), thereby blocking the ability of LPS to prime fresh neutrophils for enhanced fMLP-triggered release of superoxide. Here we show that inactivation of LPS by neutrophils was primarily due to lactoferrin. A time course for inactivating LPS showed that neutrophils (5 million/ml) took 30 min to inactivate 10 ng/ml LPS. Mononuclear cells could not inactivate LPS under the same conditions. Experiments with radioactive LPS showed that inactivated LPS remained in the medium and was not taken up or destroyed by the neutrophils during inactivation. Inactivated IPS still gelled Limulus lysate and primed monocytes. Cell-free medium from neutrophil suspensions also inactivated LPS. A single LPS-inactivating factor was purified from medium by heparin-agarose chromatography. SDS-PAGE showed a single band at 80 kDa, which was identified as lactoferrin by immunoblotting. Antilactoferrin immunoglobulin G removed the LPS-inactivating activity from purified lactoferrin and cell-free medium. Surprisingly, even purified neutrophil lactoferrin required 30 min to inactivate LPS, indicating inherently slow binding of lactoferrin to LPS J. Leukoc. Biol. 57: 865–874; 1995.
Dual function of human IgA antibodies: inhibition of phagocytosis in circulating neutrophils and enhancement of responses in IL-8-stimulated cells
Authors: Nikolova Elena B , Russell Michael W 
Published: January 2018

Abstract
We have sought to elucidate the responses of human peripheral blood neutrophils to antigenic surfaces complexed with human specific IgA antibodies obtained either as myeloma proteins that recognize staphylococcal α-toxin, or from the serum of patients with subacute bacterial endocarditis due to Streptococcus mutans, or from colostrum. In contrast to IgG, IgA antibodies bound to antigen-coated fluorescent microspheres, and subsequently exposed to complement (or not), did not promote phagocytosis, as measured by flow cytometric enumeration of cell-associated microspheres. Instead, IgA antibodies interfered with complement-dependent phagocytosis mediated by IgG antibodies. These properties were shown by different forms of IgA antibodies, including serum and secretory IgA, as well as by monoclonal or polyclonal antibodies. Neutrophils did not respond to the production of superoxide to IgA antibodies complexed with antigen-coated microspheres or with antigen deposited on a solid surface and IgA antibodies suppressed IgG antibody- and complement-mediated superoxide release. However, neutrophils pretreated with interleukin-8 ingested IgA-opsonized microspheres and released superoxide when exposed to IgA antibody-antigen complexes. IgG antibody-antigen complexes did not stimulate increased superoxide release in interleukin-8-treated neutrophils. These findings were consistent with a selective increase in the surface expression of FcoαR by interleukin-8-treated neutrophils. We conclude that IgA antibodies interfere with the phagocytic activities of normal circulating human neutrophils and may promote these activities in inflammatory neutrophils activated by interleukin-8 in which FcαR is up-regulated. J. Leukoc. Biol. 57: 875–882; 1995.
Processing of complex antigens and simple hapten-like molecules by epidermal Langerhans cells
Authors: Woods Gregory M , Henderson Kirsten G , Qu Miaomiao , Muller H Konrad 
Published: January 2018

Abstract
Langerhans cells (LCs) are antigen-presenting cells of the skin that trap small contact-sensitizing molecules and induce cutaneous hypersensitivity. LCs can present larger molecules but the mechanisms of processing have required investigation. A system combining in vitro culture of antigen with epidermal cells in the presence of inhibitors, followed by fixation and transfer of these antigen/drug-treated epidermal cells to naive mice, was developed to investigate the steps of antigen processing. Langerhans cells undertake similar, but not identical, pathways for the processing of simple and complex molecules. Complex molecules such as trinitrophenyl conjugated to ovalbumin (TNP-OVA) were internalized and modification required a chloroquine-sensitive proteolysis step and a cycloheximide-sensitive protein synthesis step. This modified product was actively recycled to the cell membrane as presentation was inhibited by blocking receptor translocation with either monensin or cytochalasin B. Small contact sensitizers such as trinitrophenyl did not undergo modification but required internalization and presentation was also inhibited by blocking receptor translocation. J. Leukoc. Biol. 57: 891–896; 1995.
Negative regulators may mediate some of the inhibitory effects of HIV-1 infected stromal cell layers on erythropoiesis and myelopoiesis in human bone marrow long term cultures
Authors: Schwartz G N , Kessler S W , Szabo J M , Burrell L M , Francisš M L 
Published: January 2018

Abstract
This report presents results concerning the potential role of negative regulators in hematopoietic suppression observed in human immunodeficiency virus (HIV)-infected long-term cultures (LTC) of human bone marrow cells. Confluent stromal cell layers established from human bone marrow cells were exposed to HIV-1ADA, a monocytotropic strain of HIV-1. A progressive increase in the concentration of HIV-1 p24 antigen in cultures exposed to HIV-1ADA demonstrated that there was a productive infection. Cells from both noninfected and HIV-infected stromal cell layers produced factors that stimulated the proliferation of colony-forming units for granulocytes and macrophages (CFU-GM) from noninfected CD34+ cells. In contrast, when noninfected CD34+ cells were directly cocultured on intact stromal cell layers fewer CFU-GM and burst-forming units for erythroid cells (BFU-E) were detected in HIV-infected LTC than in noninfected LTC. One week after the addition of CD34+ cells, the number of CFU-GM in HTV-infected LTC in six of nine experiments was reduced compared to noninfected control LTC. In those six experiments, the number of CFU-GM was only 53 ± 5% (SEM) of the number in noninfected LTC. The number of BFU-E in HIV-1-infected LTC was only 46 ± 5% of the number in noninfected LTC (n = 5). There were fewer BFU-E in HIV-1-infected LTC, whether or not there was a reduced number of CFU-GM. Neutralizing antibody to tumor necrosis factor α (TNF-α) had no effect on the number of BFU-E in HIV-infected LTC. The number of BFU-E, however, was 2.1 ± 0.2-fold greater (n = 3) in HIV-infected LTC incubated with neutralizing antibody to interferon-α. In HIV-infected LTC with decreased numbers of CFU-GM, the number of CFU-GM was approximately 2-fold greater after incubation of HIV-infected LTC with anti–interleukin-4 (IL-4). The effect of anti–TNF-α was variable, and anti–transforming growth factor-β had no effect on the number of CFU-GM in HIV-infected LTC. After 2 weeks, the number of CFU-GM in HIV-infected LTC incubated with anti–IL-4 and anti–TNF-α was 2- to 4-fold greater than in untreated HIV-infected LTC. Antibody treatment did not promote an increase in the number of CFU-GM in noninfected LTC or in LTC in which CFU-GM numbers were not reduced after HIV infection. These results demonstrate that some cells in the stromal cell layers of LTC were targets for HTV-1ADA, and that HIV-infected stromal cell layers suppressed or delayed the production of both CFU-GM and BFU-E. These results also suggest that hematopoietic suppression in HIV-infected LTC may be mediated by growth-inhibitory cytokines that are different for erythropoiesis and myelopoiesis. J. Leukoc. Biol. 57: 948–955; 1995.