bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary structure of rat CD14 and characteristics of rat CD14, cytokine, and NO synthase mRNA expression in mononuclear phagocyte system cells in response to LPS
Authors: Takai Noriyuki , Kataoka Masashi , Higuchi Yasunori , Matsuura Keiko , Yamamoto Shunsuke 
Published: January 2018

Abstract
Rat CD14 cDNA clones were isolated. The predicted protein sequence exhibits 82,61.6, and 64% identity with the mouse, rabbit, and human CD14, respectively. The levels of rat CD14 mRNA expression in resident peritoneal macrophages (PM), alveolar macrophages (AM), and peripheral blood monocytes (BM) were constitutively high, whereas that in Kupffer cells (KC) was low. On intravenous injection with lipopolysaccharide (LPS), the expression of rat CD14 mRNA in KC increased markedly, whereas the increases in PM, AM, and BM were mild. Similar features of expression of rat CD14 in these cells were observed after stimulation with LPS in vitro. The level of tumor necrosis factor α (TNF-α) mRNA expression in KC after stimulation with LPS in vivo was comparable to that in PM, AM, and BM, whereas that of TNF-α mRNA expression in KC and PM after stimulation with LPS in vitro was lower than that in AM and BM. Interleukin (IL)-1β and iNOS mRNA expressions in KC after stimulation with LPS in vivo and in vitro were low, whereas those in PM, AM, and BM were high. Little or no expression of IL-6 was observed in KC after stimulation with LPS in vivo and in vitro, whereas higher expression was observed in PM, AM, and BM than in KC.
Cellular aspects of HIV-1 infection of macrophages leading to neuronal dysfunction in in vitro models for HIV-1 encephalitis
Authors: Nottet Hans S L M , Bär Dop R , van Hassel Hans , Verhoef Jan , Boven Leonie A 
Published: January 2018

Abstract
HIV-1 is a hematogenously spread virus that most likely gains entry into the brain within blood-derived macrophages. Indeed, productive viral replication selectively occurs within perivascular and parenchymal blood-derived macrophages and microglia and HIV-infected macrophages have increased potential to bind and transmigrate through the blood-brain barrier. Once inside the brain, HIV-infected macrophages secrete a variety of proinflammatory mediators that display neuromodulatory and neurotoxic activities in several in vitro models for HIV-1 encephalitis. The final outcome regarding neuronal function and cell loss is regulated through intercellular interactions between these virus-infected cells and astrocytes. In this regard, both HIV-induced intracellular events in macrophages and interactions between HIV-infected macrophages and brain cells are reviewed as factors that might lead to neuronal injury in in vitro model systems for HIV-1 encephalitis.
Inhibition of replication of HIV in primary monocyte/macrophages by different antiviral drugs and comparative efficacy in lymphocytes
Authors: Aquaro Stefano , Perno Carlo-Federico , Balestra Emanuela , Balzarini Jan , Cenci Alessandra , Francesconi Mauro , Panti Stefania , Serra Franca , Villani Nicoletta , Caliò Raffaele 
Published: January 2018

Abstract
Several anti-HIV drugs acting on different steps of virus replication were tested in our experimental model of primary monocyte/macrophages; the results were compared with the activity found in lymphocytes. Nucleoside analogues (AZT, ddl, ddC, d4T, PMEA, 3TC etc.) show greater activity in macrophages (M/M) than in lymphocytes. In particular, the EC50 of AZT, ddC, and ddI in M/M is 2- to 100-fold lower than that found in lymphocytes. This greater efficacy of nucleoside analogues in M/M depends on the enhancement of their chain-terminating activity by the low levels of endogenous deoxynucleoside-triphosphates (dNTP) usually found in resting cells such as M/M. Non-nucleoside reverse transcriptase inhibitors (NNRTI) do not act as chain terminators (thus their antiviral effect is not related to the intracellular concentrations of dNTP); as a consequence the activity of TSAO, HEPT, TIBO, and other NNRTI tested in M/M is similar to that found in lymphocytes. Regarding inhibitors of binding and fusion of HIV, we found that their anti-HIV activity is markedly decreased (or even nullified) when M/M are treated with cytokine activators of M/M function and enhancers of HIV replication. More relevant from a clinical standpoint, protease inhibitors are able to inhibit HIV replication in chronically infected macrophages cells carrying the proviral genome already integrated in the host genome). All other inhibitors of late stage of virus life cycle tested (antisense-rev, anti-tat, interferon-α and -γ, phosphorothioate analogues, GLQ-223, etc.) were totally inactive in chronically infected macrophages. The different effects of various classes of HIV inhibitors in lymphocytes and macrophages suggests that AIDS therapy should consider all aspects of the pathogenesis of HIV infection and must be restricted to drugs, or combinations of drugs, active against both lymphocytes and M/M in all body compartments where the virus hides and replicates.
MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression
Authors: Sozzani Silvano , Introna Martino , Bernasconi Sergio , Polentarutti Nadia , Cinque Paola , Poli Guido , Sica Antonio , Mantovani Alberto 
Published: January 2018

Abstract
Monocyte chemotactic protein-1 (MCP-1) interacts with the chemokine receptor CCR2. Two CCR2 cDNAs have been described. Sequence analysis as well as Northern blotting and RNase protection with different probes revealed that the CCR2 gene is expressed in activated natural killer (NK) cells and mononuclear phagocytes as a predominant long transcript (3.4 kb) consisting of CCR2B followed by a novel sequence (X), corresponding to an intron in the genome, and by a CCR2A specific portion. The predominant long transcript is polyadenylated and present in the cytoplasm. We found that bacterial products and cytokines affect CCR2 expression. Interleukin-2 (IL-2) augmented CCR2 mRNA in monocytes and NK cells. The augmented migratory capacity of Reactivated versus resting NK cells was associated with increased CCR2 transcript levels. Lipopolysaccharide (LPS) and other microbial agents caused a rapid and drastic reduction of CCR2 mRNA levels. The rate of nuclear transcription of CCR2 was not affected by LPS, whereas the mRNA half life was reduced. These results suggest that regulation of receptor expression, in addition to agonist production, is probably a crucial point in the regulation of the chemokine system. Down-regulation of chemokine receptor expression may play a role in the modulation of HIV infection in macrophages by LPS. Levels of MCP-1 were markedly elevated in the cerebrospinal fluid (CSF) but not in blood of HIV-infected patients with cytomegalovirus (CMV) encephalitis. The CSF levels of MCP-1 in CMV encephalitis were markedly higher than those found in the CSF of HIV-infected patients with or without unrelated neurological diseases. IL-8, the prototype of C-X-C chemokines and RANTES and macrophage inflammatory protein-1α (C-C chemokines) were not substantially increased in the liquor of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurological disorders associated with HIV.
Polyribonucleotides induce nitric oxide production by human monocyte-derived macrophages
Authors: Snell Julie C , Chernyshev Olga , Gilbert Daniel L , Colton Carol A 
Published: January 2018

Abstract
Cytokine-mediated activation of inducible nitric oxide synthase (iNOS) in monocytes or macrophages is species specific. In contrast to rat or mouse, human macrophages do not produce measurable levels of nitric oxide (NO) when induced by inflammatory mediators. Exposure to noncytokine mediators such as tumor cells or viruses, however, has recently been shown to activate human iNOS. NO production in response to these mediators is much lower than that seen for rat or mouse cells and often requires several days of stimulation. We have found that the synthetic, double-stranded polyribonucleotide polyinosinic-polycytidilic acid (Poly I:C), commonly used to mimic viral exposure, activated iNOS in human monocyte-derived macrophages (MDM). The production of NO, measured by nitrite accumulation, was detected after 24 h of stimulation with Poly I:C. The single-stranded polyribonucleotide Poly I, but not Poly C, also increased NO production. Nitrite production was enhanced when the MDM were primed (pretreated) with γ or α interferon or other immune mediators such as IL-4 and was reduced by the iNOS inhibitor, N-methyl-L-arginine (L-NMMA). The use of Poly I:C to initiate NO production in human macrophages provides a useful tool to study the differences between the commonly used animal models and human cells and may provide insight into the pathophysiological significance of these differences.
Liver granulomas in schistosomiasis: mast cell-dependent induction of SCF expression in hepatic stellate cells is mediated by TNF-α
Authors: Brito José M , Borojevic Radovan 
Published: January 2018

Abstract
Mast cell proliferation, survival, and differentiation are under control of the surrounding stroma and are largely mediated by the stem cell factor (SCF). Mast cells are abundant in liver fibrosis and are proposed to be causally related with its persistence and intensity through secretion of fibrogenic cytokines. In normal adult liver, local connective tissue cells (stellate cells) do not constitutively express SCF. We studied primary cultures of stellate cells obtained from fibro-granulomatous reactions elicited in mouse liver by schistosomal infection. We have shown that the SCF expression can be induced in vitro by coculture with mast cells and this induction was dependent on the release of tumor necrosis factor α (TNF-α). Because SCF induces in mast cells proliferation and release of both fibrogenic factors and TNF-α, the described interaction between liver stroma and mast cells represents an auto-stimulatory loop, which may explain the progressive and persistent character of liver fibrosis associated with chronic inflammations or infections. Granulomatous reactions in liver elicited by chronic schistosomiasis sustain a local production of inflammatory cells, and this extramedular myelopoiesis is potentially also dependent on the induction of SCF expression in the liver stellate cells.
Immunomodulatory action of G-CSF In a rat model of endotoxin-induced liver injury: an intravital microscopic analysis of Kupffer cell and leukocyte response
Authors: Vollmar Brigitte , Messner Sven , Wanner Guido A , Hartung Thomas , Menger Michael D 
Published: January 2018

Abstract
In contrast to the anticipation that in sepsis granulocyte colony-stimulating factor (G-CSF) would overactivate the nonspecific immune system by recruiting and priming leukocytes with consequent aggravation of inflammatory tissue lesions, recombinant (r) G-CSF pretreatment was protective in various experimental non-neutropenic models of inflammation. The mechanisms of protection, however, are not fully understood. Using intravital fluorescence microscopy, we show that rG-CSF enhances leukocyte endothelial cell interaction within the microvasculature of normal rat livers, whereas rG-CSF pretreatment of animals exposed to lipopolysaccharide (LPS) attenuates the LPS-induced leukocytic response, including stasis in sinusoids as well as rolling and adherence in postsinusoidal venules with subsequent tissue infiltration. Moreover, rG-CSF, which did not affect Kupffer cell activity in normal rat livers, reduced the immediate activation of Kupffer cells on LPS exposure, as indicated in vivo by the delayed adherence/phagocytosis of intra-arterially administered latex particles associated with attenuation of proinflammatory cytokine release (tumor necrosis factor α and interleukin-6). Finally, rG-CSF reduced LPS-induced nutritive perfusion failure and hepatocellular excretory dys function. This study provides evidence for a distinct, possibly tumor necrosis factor α-dependent modulation of LPS-induced cellular response within the liver by rG-CSF, thereby achieving protection against microcirculatory perfusion failure and hepatic dysfunction. J.
Innate resistance to Listeria monocytogenes in tumor-bearing mice
Authors: Gahan Cormac G M , Barrett John R , O'Brien Michael G , O'Sullivan Gerard C , Shanahan Fergus , Collins John K 
Published: January 2018

Abstract
We have previously described the isolation, cloning, and characterization of a tumorigenic murine fibrosarcoma, designated JBS. Growth of JBS tumors in syngeneic mice initiates an antitumor immune response that initially manifests as progressive splenic hyperplasia and an increased proliferative ability in cultured splenocytes. In animals with tumors progressing beyond the 2 cm stage there is a reduction in spleen size and a gradual decrease in splenocyte proliferative abilities, leading to anergy at heavy tumor burdens (&gt;3.5 cm). During the phase of immune hyperresponsiveness in tumor-bearing mice clearance of Listeria monocytogenesby components of the innate immune system is increased. This heightened resistance to infection is most likely macrophage-mediated because these mice demonstrate an increased ability to recruit macrophages to the peritoneal cavity during Listeriainfection. In addition, these macrophages are highly activated in vivo as evidenced by an elevated capacity to express class II MHC (Ia) molecules. This increase in macrophage activation status is coincident with an increased capacity of splenocytes from tumor-bearing mice to secrete IFN-γ. In mice with much heavier tumor burdens (&gt;3.5 cm), down-regulation of the immune response leads to a reduction in peritoneal macrophage numbers, decreased macrophage Ia expression, and diminished splenic clearance of L. monocytogenes. Our data demonstrate that activation of macrophages distal to the tumor site occurs as an initial consequence of tumor growth. It is only in mice with very heavy tumor burdens that functionality of macrophages is sufficiently suppressed to allow increased splenic growth of L. monocytogenes.
Desensitization of IgE-mediated IL-4 release from human basophils
Authors: MacGlashan Donald 
Published: January 2018

Abstract
Previous studies demonstrated marked differences in the time course of interleukin-4 (IL-4) and histamine release, implying different mechanisms of desensitization. To explore this possibility basophils were desensitized with anti-IgE antibody by treating the cells for various periods of time in the absence of extracellular calcium (Cae). The basophil response following addition of Cae was assessed by measuring IL-4 or histamine release by measuring the cytosolic calcium response ([Ca2+]i). The kinetics of desensitization for IL-4 and histamine release did not differ; 50% desensitization occurred at 37 ± 8 and 29 ± 16 min for IL-4 and histmaine release, respectively. The kinetics of desensitization as assessed by the [Ca2+]i response was found to be biphasic; an initial enhancement of the [Ca2+]i response after 5–15 min of desensitization was followed by a rapid decrease so that by 30 min the amount of desensitization was equivalent to that observed for histamine release. Other than this initial period of enhanced calcium response, desensitization kinetics were unexpectedly similar for all measured endpoints. These results suggest that, during stimulation in the absence of Cae, there is a down-regulation process that influences all events on a similar time scale. Because the time scales for secretion of histamine, LTC4 or IL-4 or the [Ca2+]iresponse markedly differ (i.e., stimulation in the presence of Cae), these results also indicate that down-regulatory processes differ depending on the presence or absence of Cae.
Two distinct Ca2+ storage and release sites in human neutrophils
Authors: Pettit Elizabeth J , Hallett Maurice B 
Published: January 2018

Abstract
It is well established that changes in cytosolic free Ca2+ play a role in a number of neutrophil responses such as cell shape change and oxidase activation. The release of intracellular stored Ca2+ occurs with stimuli that either act by occupancy of seven membrane-spanning domain receptors or those which act by receptor cross-linking. Here, two distinct Ca2+ storage and release sites have been identified in neutrophils. Using chlortetracycline fluorescence as an indicator of Ca2+ storage, two separate Ca2+ storage sites have been identified. One site was located peripherally under the plasma membrane and the other was in the juxtanuclear space. Confocal imaging of Fluo3-loaded neutrophils demonstrated that the central Ca2+ storage site released Ca2+ in response to N-formyl-methionyl-leucyl-phenylalanine, whereas engagement and clustering of CD11b/CD18 integrins causes Ca2+ release from the peripheral stores. The release sites also correlated with organelles that stained with DiOC6(3). Localized phototoxicity generated by DiOC6(3) excitation resulted in inhibition of the release of stored Ca2+, which was selective for the stimulus used. The presence of two distinct cellular locations for these Ca2+ stores and their independent release raises the possibility that separate intracellular messengers for their release are generated.
Pattern of inheritance in hereditary myeloperoxidase deficiency associated with the R569W missense mutation
Authors: Nauseef W M , Cogley M , Bock S , Petrides P E 
Published: January 2018

Abstract
Myeloperoxidase (MPO) is an essential component of the oxygen-dependent microbicidal system of neutrophils and monocytes. Hereditary deficiency of MPO occurs in 1 in 2,000 to 4,000 individuals in the general population and has been generally considered an autosomal recessive trait. Previous studies have used the peroxidase activity of blood leukocytes to assess the phenotype of affected family members. Eosinophil peroxidase (EPO) also contributes to the peroxidase activity of blood leukocytes. Because EPO expression is normal in MPO-deficient subjects, eosinophil contamination can significantly contribute to peroxidase activity in leukocytes from family members of an MPO-deficient subject and thereby undermine correct interpretation of the inheritance pattern. To avoid this potential problem, we used cytochemical, immunochemical, and genetic techniques to assess the inheritance pattern of MPO deficiency in sixteen individuals from five unrelated kindreds. Each kindred had an index case with MPO deficiency and the R569W missense mutation, a genotype that causes MPO deficiency. Our analysis demonstrated that MPO deficiency was not inherited as a simple autosomal recessive trait. Most subjects were compound heterozygotes with respect to the R569W mutation and demonstrated a spectrum of phenotypes. Our data demonstrate the broad phenotypic impact of compound heterozygosity on the expression and function of a multimeric protein such as MPO.
Identification of glyceraldehyde-3-phosphate dehydrogenase as a Ca2+-dependent fusogen in human neutrophil cytosol
Authors: Hessler Ronald J , Blackwood R Alexander , Brock Thomas G , Francis Joseph W , Harsh Donna M , Smolen James E 
Published: January 2018

Abstract
The membrane fusion events observed during neutrophil degranulation are important aspects of the immunoregulatory system. In an attempt to understand the regulation of granule-plasma membrane fusion, we have begun characterizing human neutrophil cytosol for fusion activity, finding that 50% of the fusogenic activity could be attributed to members of the annexin family of proteins. The major non-annexin fusion activity (25% of the total cytosolic activity) was enriched by ion exchange chromatography after depletion of annexins by Ca2+-dependent phospholipid affinity chromatography. The fusion activity co-purified with a 10,14-kDa dimer identified as leukocyte L1 (which was non-fusogenic), along with an approximately 36-kDa protein. This protein was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by amino-terminal sequencing, and the fusion activity was verified using commercially available GAPDH. GAPDH may play an important role in degranulation because it is as potent as annexin I on a mass basis and may constitute up to 25% of the total cytosolic fusion activity of the neutrophil.
Interleukin-5 binds to heparin/heparan sulfate. A model for an interaction with extracellular matrix
Authors: Lipscombe Richard J , Nakhoul Anne-Marie , Sanderson Colin J , Coombe Deirdre R 
Published: January 2018

Abstract
Interleukin-5 (IL-5) is the major cytokine regulating eosinophil production. In allergic disease tissue damage is primarily caused by eosinophils. Heparan sulfate proteoglycans are components of the bone marrow stroma, which supports hemopoietic cell differentiation and proliferation. We show that at low IL-5 concentrations heparan sulfate enhances the proliferation of an IL-5-dependent cell line. To investigate a mechanism for this effect we used an artificial proteoglycan to establish an enzyme-linked immunosorbent assay for the binding of heparin to proteins. Using this assay we demonstrate that IL-5 binds to heparin. The IL-5/heparin interaction is inhibited by ethylenediaminetetraacetate and enhanced by low concentrations of zinc ions. IL-5 interacts with iduronic acid containing glycosaminoglycans, and heparan sulfate preparations that have numerous N-sulfated domains per chain are especially efficient at inhibiting heparin binding. Both IL-5/ heparin binding and the synergistic effect of IL-5 and heparan sulfate on cell proliferation were inhibited by an anti-IL-5 monoclonal antibody. These data suggest that the binding of IL-5 to heparan sulfate modulates IL-5 activity.
Role of chemokines and cytokines in a reactivation model of arthritis in rats induced by injection with streptococcal cell walls
Authors: Schrier D J , Schimmer R C , Flory C M , Tung D K-L , Ward P A 
Published: January 2018

Abstract
Intraarticular injection of streptococcal cell wall (SCW) antigen followed by intravenous challenge results in a T cell-mediated monoarticular arthritis in female Lewis rats. Initial studies showed that this reactivation response to intravenous SCW antigen is dependent on the presence of interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) and that the early phase of swelling is neutrophil-dependent. Neutrophil depletion or passive immunization with antibodies to P-selectin or macrophage inflammatory protein-2 reduced the intensity of ankle edema and the influx of neutrophils. After the first few days, however, the arthritic response is mediated primarily by mononuclear cells. Joint tissues showed up-regulation of mRNA for monocyte chemotactic protein-1 (MCP-1), which could be inhibited in part by anti-IL-4; treatment of rats with antibodies to IL-4 or MCP-1 significantly suppressed development of ankle edema and histopathological evidence of inflammation. Antibodies to interferon-γ or IL-10 had no effect. Treatment with anti-MCP-1 also suppressed influx of 111In-labeled T cells into the ankle joint. These data suggest that the late, mononuclear-dependent phase of SCW-induced arthritis in female Lewis rats requires cytokines that up-regulate MCP-1, which in turn may facilitate recruitment and extravasation of mononuclear cells into the joint.