bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of rat macrophages by Betafectin PGG-glucan requires cross-linking of membrane receptors distinct from complement receptor three (CR3)
Authors: Michalek Michael , Melican David , Brunke-Reese Deborah , Langevin Matthew , Lemerise Kristen , Galbraith William , Patchen Myra , Mackin William 
Published: January 2018

Abstract
PGG-glucan (Betafectin ) is a soluble, highly purified yeast (1,3)-β-glucan with broad anti-infective and immunomodulatory activities. These studies evaluated the ability of PGG-glucan to directly elicit O2– and tumor necrosis factor α (TNF-α) production by rat leukocytes in vitro. Particulate β-glucan stimulated O2– production by the rat NR8383 alveolar macrophage cell line and resident rat peritoneal macrophages, but soluble PGG-glucan did not. In contrast, presentation of PGG-glucan to cells after covalent immobilization to a plastic surface caused a direct stimulation of O2– and TNF-α production. The O2– response of rat leukocytes to immobilized PGG-glucan was inhibited by soluble PGG-glucan, indicating that cellular responses to both immobilized and soluble PGG-glucan occur via common cell surface receptors. Because complement receptor type three (CR3) has been proposed as a β-glucan receptor on human leukocytes, NR8383 cells were evaluated for the presence of CR3. Indirect immunofluorescence and flow cytometric analysis showed that despite being responsive to both particulate and immobilized β-glucans, NR8383 cells expressed no detectable CR3. These results indicate that the β-glucan receptors on NR8383 cells are not CR3 and suggest that physical presentation plays an important role in inducing proinflammatory leukocyte responses to PGG-glucan. J. Leukoc. Biol. 64: 337–344; 1998.
Lipopolysaccharide-stimulated TNF-α release from cultured rat Kupffer cells: sequence of intracellular signaling pathways
Authors: Lichtman Steven N , Wang Jian , Lemasters John J 
Published: January 2018

Abstract
We recently hypothesized that lipopolysaccharide (LPS) stimulation of rat Kupffer cells to induce tumor necrosis factor α (TNF-α) release requires internalization of LPS, acidification of endosomes, elevation of intracellular calcium, protein kinase C (PKC) activation, and protein tyrosine kinase (PTK) activation. This study uses inhibitors in pulse-chase experiments to determine the sequence of events of intracellular signals required for LPS-stimulated TNF-α release from Kupffer cells. Inhibitors of internalization (cytochalasin B, monodansylcadaverine) prevented LPS-stimulated TNF-α release when added simultaneously with LPS but when added 10 min after LPS, no significant inhibition occurred. The inhibitor of PTK, tyrphostin AG, blocked TNF-α release by only 39 ± 4% (P &lt; 0.001 compared with TNF-α release when added simultaneously with LPS) when added 10 min after LPS. Inhibitors of endosomal acidification (bafilomycin A, monensin) inhibited LPS-stimulated TNF-α release by 92 ± 11% (P &lt; 0.001 when no inhibitor was used) when added 10 min after LPS and their effect was totally abrogated when added 45 min after LPS. The PKC inhibitor, H-7, blocked TNF-α release by 94 ± 9% (P &lt; 0.001 when no inhibitor was used) when added 30 min after LPS. The calcium channel blocker, nisoldipine, still inhibited LPS-stimulated TNF-α release when added 45 min after LPS. These data support the hypothesis that for LPS-stimulated TNF-α release in Kupffer cells, LPS must first be internalized, which may stimulate PTK activation. An intermediate step of signaling involves endosomal acidification. Elevation of intracellular calcium and PKC activation occur as late intracellular signaling events. J. Leukoc. Biol. 64: 368–372; 1998.
Contribution of the CXC chemokines IP-10 and Mig to the antitumor effects of IL-12
Authors: Kanegane Chiharu , Sgadari Cecilia , Kanegane Hirokazu , Teruya-Feldstein Julie , Yao Lei , Gupta Ghanshyam , Farber Joshua M , Liao Fang , Liu Li , Tosato Giovanna 
Published: January 2018

Abstract
The mechanisms by which interleukin-12 (IL-12) exerts antitumor effects have been difficult to dissect. In this study, we examined the potential contribution of the chemokines interferonγ-inducible protein-10 (IP-10) and Mig to the antitumor effects of IL-12. Using an athymic mouse model, local inoculations with IL-12 consistently produced tumor size reductions associated with characteristic tumor necrosis and vascular damage. These effects were indistinguishable from those produced by IP-10 or Mig injected locally in the same tumor model. Local and systemic treatment with IL-12 was associated with expression of the interferon-γ (IFN-γ), IP-10, and Mig genes and proteins in the tumor. Levels of IP-10 and Mig expression in the tumor, the liver, and the kidney were inversely correlated with tumor size. Administration in vivo of neutralizing antibodies to IP-10 and Mig reduced substantially the antitumor effects of IL-12 inoculated locally into the tumors. These results support the notion that IP-10 and Mig contribute to the antitumor effects of IL-12 through their inhibitory effects on tumor vasculature. J. Leukoc. Biol. 64: 384–392; 1998.
Leukocyte trafficking in experimental autoimmune uveitis in vivo
Authors: Parnaby-Price Adrian , Stanford Miles R , Biggerstaff John , Howe Lucy , Whiston Roy A , Marshall John , Wallace Graham R 
Published: January 2018

Abstract
Leukocyte trafficking from blood into tissue is a fundamental process in immune surveillance and the immune response to stimuli. Experimental autoimmune uveitis (EAU) is an animal model for posterior uveitis and is mediated by T lymphocytes and macrophages that infiltrate the posterior segment of the eye. To analyze leukocyte migration into retinal tissue during the course of EAU, labeled cells were identified in vivo by scanning laser ophthalmoscopy and in retinal flat-mounts by confocal microscopy. Adhesion of blood leukocytes to retinal endothelial cells in vivo was significantly raised 48 h before the appearance of clinical disease, and this correlated with the increased expression of CD54 on retinal vessels. Mitogen-activated spleen cells and CD4+ T cells only entered into retinal tissue in animals with clinical disease and not naive recipients. The disease status of the donor animal had no effect on leukocyte trafficking. These results, which identify leukocyte-endothelial cell interactions in vivo, suggest that the activation of the retinal endothelium is a prerequisite to leukocyte adhesion and extravasation into ocular tissue during EAU. J. Leukoc. Biol. 64: 434–440; 1998.
Genetic and immunological parameters governing in vivo susceptibility/resistance to retrovirally induced murine malignant histiocytosis
Authors: Panoskaltsis-Mortari Angela , Egeler R Maarten , Yaeger Thomas M , Yoneji Sumiko , Schmitz Laura , Lilly Frank , Nesbit Mark E , Blazar Bruce R 
Published: January 2018

Abstract
Malignant histiocytosis sarcoma virus (MHSV) arose as a recombinant of c-Harvey-ras murine sarcoma virus (Ha-MuSV) and Friend mink cell focus-forming virus (F-MCFV). It is a defective acute transforming retrovirus that, along with Friend murine leukemia helper virus (F-MuLV), induces malignant histiocytosis (MH) in susceptible adult mice. We have assessed the in vivo susceptibility to MHSV in inbred homozygous, F1 hybrid, congenic, and recombinant inbred (RI) mice. We have shown that: (1) in vivo resistance to MHSV is multigenic, regulated by MHC and non-MHC genes in a different fashion than with F-MCFV, F-MuLV, or Ha-MuSV; (2) using BXD RI mice, the resistance phenotype is linked with 95.8% probability to two linked loci, Pmv-9 and Iapls3-14, on chromosome 13 (homologous to the area of human chromosome 5 for which a chromosomal break point at position 5q35 is associated with human MH); and (3) CD4+ T cells are critical for MHSV resistance. J. Leukoc. Biol. 64: 441–450; 1998.
Ionizing radiation potentiates the induction of nitric oxide synthase by IFN-γ and/or LPS in murine macrophage cell lines: role of TNF-α
Authors: McKinney Leslie C , Aquilla Elizabeth M , Coffin Deborah , Wink David A , Vodovotz Yoram 
Published: January 2018

Abstract
Macrophages are activated to become cytotoxic by a highly coordinated set of cytokine signals. Ionizing radiation can mimic cytokine signals and lead to enhanced states of activation. We tested the ability of γ-radiation, alone and with interferon-γ (IFN-γ) and/or lipopolysaccharide (LPS), to induce nitric oxide (NO) production in J774.1 and RAW264.7 murine macrophages. NO was induced weakly, moderately, or strongly by IFN-γ alone, LPS alone, or IFN-γ + LPS, respectively. Radiation alone (0.5–50 Gy) did not induce NO, but enhanced NO production in a dose-dependent manner (0.5–5 Gy) when cells were exposed to IFN-γ or LPS 24 h post-irradiation. Immunoblots showed parallel induction of nitric oxide synthase (NOS2). Application of antitumor necrosis factor α (TNF-α) antibody before irradiation blocked induction of NO by IFN-γ. We conclude (1) that irradiated cells produce more NO in response to either IFN-γ or LPS and (2) that the increase is mediated by induction of TNF-α. J. Leukoc. Biol. 64: 459–466; 1998.
Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules
Authors: Grassi Fernanda , Dezutter-Dambuyant Colette , McIlroy Dorian , Jacquet Christelle , Yoneda Kozo , Imamura Sadao , Boumsell Laurence , Schmitt Daniel , Autran Brigitte , Debre Patrice , Hosmalin Anne 
Published: January 2018

Abstract
Most monocyte-derived dendritic cells (DC) display CD1a, like Langerhans cells (LC) and some dermal DC, but their relationship with these skin DC remains unclear. To address this issue, we studied the expression of different antigens characteristic of skin DC and of monocyte/macrophages in CD1a+ and CD1a– monocyte-derived DC. Their phenotype indicated that they may be related to dermal DC rather than to LC, i.e., they were all CD11b-positive, and 72% were Factor XIIIa-positive, but they did not express E-cadherin nor VLA-6. It is interesting that CD1a+ and CD1a– cells showed intracytoplasmic granules that were different from LC Birbeck granules. These pheno-typical and ultrastructural features are comparable to those of CD14-derived DC obtained from cord blood precursors [C. Caux et al. J. Exp. Med. 184, 695–706]. These results show a close relationship between these two in vitro models, which are both related to dermal DC. J. Leukoc. Biol. 64: 484–493; 1998.
The role of IL-5 in bleomycin-induced pulmonary fibrosis
Authors: Gharaee-Kermani Mehrnaz , McGarry Bridget , Lukacs Nicholas , Huffnagle Gary , Egan Robert W , Phan Sem H 
Published: January 2018

Abstract
Eosinophils are known to express cytokines capable of promoting fibrosis. Interleukin-5 (IL-5) is important in regulating eosinophilopoiesis, eosinophil recruitment and activation. Lung IL-5 expression is elevated in pulmonary fibrosis, wherein the eosinophil is a primary source of fibrogenic cytokines. To determine the role of IL-5 in pulmonary fibrosis, the effects of anti-IL-5 antibody were investigated in a model of bleomycin-induced pulmonary fibrosis. Fibrosis was induced in mice by endotracheal bleomycin treatment. Animals were also treated with either anti-IL-5 antibody or control IgG. Lungs were then analyzed for fibrosis, eosinophil influx, chemotactic activity, and cytokine expression. The results show that a primary chemotactic activity at the height of eosinophil recruitment is IL-5. Furthermore, anti-IL-5 antibody caused significant reduction in lung eosinophilia, cytokine expression, and fibrosis. These findings taken together suggest an important role for IL-5 in pulmonary fibrosis via its ability to regulate eosinophilic inflammation, and thus eosinophil-dependent fibrogenic cytokine production. J. Leukoc. Biol. 64: 657–666; 1998.
β1 Integrin-dependent binding of Jurkat cells to fibronectin is regulated by a serine-threonine phosphatase
Authors: Seminario Maria-Cristina , Sterbinsky Sherry A , Bochner Bruce S 
Published: January 2018

Abstract
We investigated the effects of signaling molecule inhibitors on the expression and function of β1 integrins in Jurkat cells. Jurkat cells expressed α4β1 and α5β1, with significant levels of constitutively activated β1 integrins as assessed by labeling with mAb 15/7 that distinguishes between activation states. Adhesion to fibronectin (Fn) was mediated equally through α4 and α5 subunits, and was potentiated by the β1 integrin activating mAb 8A2. Fn adhesion was decreased by okadaic acid through effects on both α4β1 and α5β1. Tyrphostin A23 also decreased adhesion but was less potent. Neither inhibitor had any effect on the surface expression of total or activated β1 integrins. The effect of tyrphostin was completely reversed by 8A2; the effect of okadaic acid was only partially reversed. Using Calyculin A, we determined that Jurkat adhesion to Fn was regulated via protein phosphatase 1, independent of the levels of integrins or integrin activation epitopes. Activation of Jurkat cells with a CD3-stimulating mAb enhanced adhesion to Fn and was partially blocked by okadaic acid. These data demonstrate different regulatory pathways for constitutive versus activation-dependent adhesion via β1 integrins, and implicate both tyrosine kinases and serine-threonine phosphatases in integrin function. J. Leukoc. Biol. 64: 753–758; 1998.
The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38
Authors: Ferrero Enza , Malavasi Fabio 
Published: January 2018

Abstract
Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of expression in leukocytes, although evidence is accumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a member of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nature. Functionally, CD38 is an eclectic molecule with the ability not only to catalyze but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan, and to other ligands. Interaction with CD38 on various leukocyte subpopulations has profound though diverse consequences on their life-span, but these effects seem to be independent of the enzymatic activity of the molecule. CD38 challenges our expectations of a surface molecule and we must sift through its many guises to unmask its true nature. J. Leukoc. Biol. 65: 151–161; 1999.
Macrophages interact with enriched populations of distinct T lymphocyte subsets for the induction of severe destructive Lyme arthritis
Authors: DuChateau Brian K , Munson Erik L , England Douglas M , Lovrich Steven D , Callister Steven M , Jensen Jani R , Schell Ronald F 
Published: January 2018

Abstract
Severe destructive Lyme arthritis was detected in the hind paws of hamsters infused with enriched populations of either CD4+ or CD4- T lymphocytes along with macrophages exposed in vitro to formalin-inactivated Borrelia burgdorferi and then infected with the Lyme spirochete. Swelling was detected 4 days after infection, increased rapidly, peaked on day 8 of infection, and gradually decreased. Similarly, severe destructive arthritis was induced in hamsters infused with enriched populations of unfractionated T lymphocytes and macrophages exposed to spirochetes after infection with B. burgdorferi. Histopathological examination affirmed that hamsters infused with CD4+, CD4-, or unfractionated T lymphocytes and macrophages exposed to B. burgdorferi-induced arthritis. In addition, macrophages exposed in vitro to B. burgdorferi demonstrated both conventional and coiling phagocytosis, suggesting a mechanism by which CD4+ and CD4- T lymphocytes induce arthritis, respectively. These findings demonstrate that both CD4+ and CD4- subpopulations of T lymphocytes are capable of interacting with macrophages for the induction of severe destructive Lyme arthritis. J. Leukoc. Biol. 65: 162–170; 1999.
Chemokine-induced phosphorylation of CC chemokine receptor 5 (CCR5)
Authors: Olbrich Heike , Proudfoot Amanda E I , Oppermann Martin 
Published: January 2018

Abstract
The CC-chemokine receptor 5 (CCR5) mediates activation of T lymphocytes and macrophages by chemokines and is a major co-receptor for macrophage-tropic HIV-1 strains. Recently, it was shown that the natural CCR5 ligands RANTES, macrophage inflammatory protein-1á (MIP-1á), MIP-1β, and amino-terminal modifications of RANTES (Met-RANTES, AOP-RANTES) significantly differ in their abilities to induce sequestration of CCR5 from cellular surfaces. It was hypothesized that these findings may account for the observed differences between these molecules to inhibit HIV infectivity in vitro. Herein we review our work on early regulatory mechanisms that are initiated by ligand binding to CCR5 and that, conceptually, are involved in receptor endocytosis. A better understanding of these mechanisms may provide new therapeutic strategies to prevent HIV infection. J. Leukoc. Biol. 65: 281–285; 1999.
Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons
Authors: Dickensheets Harold L , Donnelly Raymond P 
Published: January 2018

Abstract
The Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including Fc∊RIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-α and IFN-β) and type Ii interferon (IFN-γ) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose-and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-β and IFN-γ to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression. J. Leukoc. Biol. 65: 307–312; 1999.
Sphingosine 1-phosphate: a prototype of a new class of second messengers
Authors: Spiegel Sarah 
Published: January 2018

Abstract
Sphingosine 1-phosphate (SPP) is an important sphingolipid-derived second messenger in mammalian cells that acts to promote proliferation and to inhibit apoptosis. Various growth factors increase the intracellular concentration of SPP by activating sphingosine kinase, the molecular cloning of which has revealed that it defines a new type of lipid kinase. Cell fate is influenced by the balance between the intracellular concentration of SPP and that of ceramide, a pro-apoptotic sphingolipid metabolite. The observation that a similar “rheostat” is a determinant of cell survival in yeast cells exposed to heat shock indicates that it is an evolutionarily conserved mechanism of stress regulation. SPP also acts extracellularly to inhibit cell motility and to influence cell morphology, effects that appear to be mediated by the G protein-coupled receptor EDG1. These observations indicate that SPP is the prototype of a new class of lipid mediators that exert both intracellular and extracellular actions. J. Leukoc. Biol. 65: 341–344; 1999.
Insights into the neurodegenerative process of Alzheimer's disease: a role for mononuclear phagocyte-associated inflammation and neurotoxicity
Authors: Cotter Robin L , Burke William J , Thomas Vince S , Potter Jane F , Zheng Jialin , Gendelman Howard E 
Published: January 2018

Abstract
Since the first description of Alzheimer's disease (AD) in 1907, significant progress was made into understanding disease pathophysiology. The enormous effort in AD research has translated into the discovery of genetic linkages for disease, into elucidating the structure and function of the etiologic β-amyloid protein, and into unraveling the seemingly complex neuroimmunological cascade that affects neuronal dysfunction. Although effective therapies do not currently exist, many are being developed. We propose that the neuropathogenesis of AD, in measure, revolves around the immunological activation of glial cells, which in turn leads to alterations in inflammatory neurotoxin production, and ultimately to neuronal injury and death. Elucidating the mechanisms involved in such glial cell immune activation should provide valuable insights into understanding the disease process and in providing effective therapeutics to prevent and/or retard the devastating neurodegeneration that afflicts so many of our elderly. J. Leukoc. Biol. 65: 416–427; 1999.
HIV-1-induced neuronal injury in the developing brain
Authors: Epstein Leon G , Gelbard Harris A 
Published: January 2018

Abstract
HIV-1 infection of the nervous system causes neuronal injury and death, resulting in cognitive, motor, and behavioral dysfunction in both adults and children. In infants a characteristic feature of HIV-1 infection is impaired brain growth resulting in secondary microcephaly with onset between 2 and 4 months of age. This post-natal period of brain development is particularly vulnerable to excitotoxic neuronal injury due to the active synaptogenesis and pruning that takes place at this age associated with over-expression of excitatory amino acid (EAA) receptors. HIV-1 infection of brain microglia and perivascular macrophages results in chronic inflammation manifest pathologically as diffuse microglial activation and reactive astrogliosis. Several inflammatory products of activated microglia, including tumor necrosis factor a (TNF-α) and platelet-activating factor (PAF) have been shown to act as neuronal toxins. This toxic effect can be antagonized by blocking NMDA (or AMPA) glutamate receptors, suggesting that (weak) excitotoxicity leads to oxidative stress, neuronal injury, and apoptosis. HIV-1 infection and chronic inflammation may also contribute disruption of the blood–brain barrier and could result in further entry into the CNS of toxic viral or cellular products or additional HIV-1-infected cells. We hypothesize that prolonged microglial activation during HIV-1 infection underlies the neuronal injury and impaired brain growth in affected infants. Further investigation of the interaction between HIV-1- infected/activated microglia and developing neurons seems warranted. The current understanding of HIV neuropathogenesis implies that therapeutic strategies should target the sustained immune activation in microglia, attempt to repair the integrity of the blood-brain barrier, and provide “neuroprotection” from excitotoxic neuronal injury. J. Leukoc. Biol. 65: 453–457; 1999.