bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential screening identifies genetic markers of monocyte to macrophage maturation
Authors: Krause Stefan W , Rehli Michael , Kreutz Marina , Schwarzfischer Lucia , Paulauskis Joseph D , Andreesen Reinhard 
Published: January 2018

Abstract
Maturation of cells of the mononuclear phagocyte lineage from bone marrow precursors to tissue macrophages (MAC) via circulating blood monocytes (MO) is a multistep process only partially understood. Similarly, MAC differentiation can be observed if MO are cultured in vitro. In an attempt to further characterize molecular changes occurring during this process we carried out differential screening of a MO-derived MAC cDNA library using MO and MAC cDNA. After subcloning and confirmation by a second round of screening, partial sequencing of 41 cDNA clones was performed. In 33 clones the sequences of 7 different previously identified cDNAs were found. The mRNA expression of two of the corresponding genes (apolipoprotein E, ferritin light chain) is already known to be up-regulated during MAC maturation. For one gene (cathepsin B), a specific up-regulation of mRNA expression could be shown corresponding to previous protein data. For four genes [human cartilage glycoprotein (HC-gp39), osteopontin, type IV collagenase, and tryptophanyl-tRNA synthetase] the specific expression in MAC versus MO was previously unknown but could be confirmed by the use of Northern blot analysis. Of these genes, HC-gp39 is especially interesting because it is only expressed during the late stages of MAC differentiation.
Augmented expression of platelet-activating factor receptor gene by TNF-α through transcriptional activation in human monocytes
Authors: Dagenais Pierre , Thivierge Maryse , Parent Jean-Luc , Stankova Jana , Rola-Pleszczynski Marek 
Published: January 2018

Abstract
Tumor necrosis factor α (TNF-α) is a cytokine produced by activated monocytes and often associated with platelet-activating factor (PAF) during the pathogenesis of many inflammatory and infectious diseases. PAFR is a G-protein-coupled receptor constitutively expressed on monocytes. TNF-α (100–400 U/mL) significantly increased PAFR mRNA expression in human monocytes. This increase was seen after 1 h of stimulation and persisted up to 24 h. Actinomycin D pretreatment studies revealed a transcriptional increase in PAFR gene expression without effect on mRNA half-life. [3H]WEB 2086 binding studies showed a significant (43%) increase in specific binding sites in 24-h-treated cells without change in receptor affinity. Increased interleukin-6 production in response to PAF was also found in 24-h TNF-α-pretreated monocytes. These observations provide new evidence for TNF-α and PAF interactions in human monocytes during inflammatory processes through up-regulation of PAFR expression by TNF-α.
Marked inhibition of the intracellular multiplication of Legionella pneumophila in monocytes isolated from carriers of human T lymphotropic virus type I
Authors: Funai Noriko , Shimamoto Yoshinori , Watanabe Masayuki , Yoshida Shin-lchi , Kohashi Osamu 
Published: January 2018

Abstract
Intracellular growth patterns of Legionella pneumophila were examined In monocytes obtained from carriers of human T-lymphotropic virus type I (HTLV-1) and controls who were HTLV-1 seronegative. All subjects were seronegative for antibodies against L. pneumophila. Bacterial growth was determined 0, 1, 2, and/or 3 days after infecting peripheral blood mononuclear cells (PBMCs) with the bacteria. The intracellular growth of L. pneumophila was markedly inhibited in HTLV-1 carriers compared with normal controls. When the lymphocytes were depleted from the HTLV-1 carrier PBMC cultures before infection, this inhibition was abolished. Inhibition reappeared, however, when the 72-h culture supernatants of PBMCs from HTLV-1 carriers were added to the lymphocyte-depleted cultures. Culture supernatants of infected and uninfected PBMCs from HTLV-1 carriers exhibited markedly increased levels of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) compared with the HTLV-1 seronegative controls. In the HTLV-1 carriers, IFN-γ was produced by the CD4+ lymphocytes, whereas TNF-α was secreted by the monocytes. Addition of anti-IFN-γ or anti-TNF-α antibodies to the HTLV-1 carrier PBMC cultures diminished the inhibition of intracellular growth of L. pneumophila. Results suggest that the monocytes are activated in HTLV-1 carriers. These findings may explain why an opportunistic infection by certain intracellular pathogens is rarely seen among HTLV-1 carriers.
Studies on the mechanisms involved in antigen-evoked pleural inflammation in rats: contribution of IgE and complement
Authors: Lima Marcia C R , Prouvost-Danon Annie , e Silva Patricia M R , Chagas Maria do Socorro S , Calheiros Andrea S , Cordeiro Renato S B , Latine Dominique , Bazin Hervé , Ryan Una S , Martins Marco A 
Published: January 2018

Abstract
Immunoglobulin E (IgE) has been shown to play a critical role in the allergic late-phase reaction, which is marked by intense leukocyte infiltration and edema. In this study we assessed the allergic pleural inflammation triggered by intrapleural (i.pl.) challenge in sensitized rats. We examined pleural effluent from actively sensitized rats following anti-IgE monoclonal antibody (mAb) (MARE-1) provocation for protein exudation, neutrophil as well as eosinophil accumulation. Inflammatory changes triggered by antigen after passive sensitization with IgE mAb was also assessed for comparison. Total serum level of IgE was found to be about threefold increased 7–8 days post-active sensitization, remaining augmented for at least 30 days. Increased levels of peritoneal leukocyte-bound IgE and serum IgE with specificity to ovalbumin were also detected. Nevertheless, the anti-IgE challenge in 14-day actively sensitized was shown to be a weak stimulus of neutrophil and eosinophil accumulation, despite being able to cause intense protein extravasation. Similarly, antigen challenge of IgE-passively sensitized rats caused protein leakage that was comparable to that induced by anti-IgE mAb in actively sensitized rats but led to a much lower neutrophil/eosinophil infiltration. Also, blockade of complement with recombinant human soluble C receptor-1 (sCR1) treatment prevented actively sensitized rats from reacting to antigen with neutrophil and eosinophil recruitment without modifying protein extravasation. These data suggest that IgE and complement-mediated mechanisms probably account for the exudation and leukocyte infiltration that is characteristic of the pleural inflammatory response observed in actively sensitized rats.
Osteoclasts, macrophages, and the molecular mechanisms of bone resorption
Authors: Teitelbaum Steven L , Tondravi M Mehrdad , Ross F Patrick 
Published: January 2018

Abstract
The osteoclast is a physiological polykaryon and the major if not exclusive resorptive cell of bone. It participates in bone remodeling, repair, and growth and mobilization of mineral to meet homeostatic demands. Most importantly, osteoporosis, a disease endemic in Western society and Asia, is always a reflection of enhanced osteoclastic activity relative to bone formation by osteoblasts. In fact, all forms of antiosteoporosis therapy proven successful involve inhibition of osteoclastic bone resorption. Bone resorption is regulated either by altering recruitment of osteoclast precursors into fully differentiated resorptive polykaryons or modulating the rate at which mature osteoclasts degrade bone. With this in mind, our laboratory has focused on the molecular mechanisms of osteoclast differentiation and the means by which the cell degrades bone matrix.
Defects in intracellular oxidative metabolism of neutrophils undergoing apoptosis
Authors: Narayanan P K , Ragheb K , Lawler G , Robinson J P 
Published: January 2018

Abstract
Apoptosis permits neutrophil recognition by macrophages, thereby not only limiting potential cytotoxicity but also promoting resolution of inflammation. A direct relationship between apoptosis and intracellular hydrogen peroxide (H2O2) production was observed in phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils aged in culture. A significant decrease in intracellular H2O2 production was observed in aging neutrophils at 12,24, and 48 h. However, intracellular superoxide anion production in response to PMA stimulation was preserved up to 24 h, implying retention of intracellular signaling pathways leading to NADPH oxidase stimulation. A significant decrease in the cytoplasmic content and activity of Cu,Zn superoxide dismutase was responsible for the observed decline in intracellular H2O2 production in apoptotic neutrophils. Intracellular glutathione content also decreased concomitantly with H2O2 production. These observations indicate that onset of apoptosis in neutrophils is in part mediated by oxidative stress resulting from the down-regulation of key antioxidant defense systems of the cell, namely superoxide dismutase and glutathione.
Random migration of polymorphonuclear leukocytes induced by GM-CSF involving a signal transduction pathway different from that of fMLP
Authors: Harakawa Nari , Sasada Masataka , Maeda Akinori , Asagoe Kohsuke , Nohgawa Masaharu , Takano Kuniko , Matsuda Yuzuru , Yamamoto Kokichi , Okuma Minoru 
Published: January 2018

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) Induced random migration of human polymorphonuclear leukocytes (PMNs) but not chemotaxis. Chemoattractants such as N-formylmethionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and interleukin-8 (IL-8) induced both random migration and chemotaxis. Other inflammatory cytokines, including granulocyte colony-stimulating factor (G-CSF), interleukin 1α (IL-1α), and tumor necrosis factor α (TNF-α), did not induce either movement. One-minute exposure of PMNs to GM-CSF was sufficient for the induction of random migration, whereas fMLP-induced random migration required continued presence of fMLP. Inhibitors of phosphatidylinositol 3-kinase (PI3-K), protein kinase C (PKC), and protein tyrosine kinase (PTK) had no effect on random migration induced by GM-CSF, whereas fMLP-induced movements were partially inhibited by PTK inhibitors but not by inhibitors of PI3-K inhibitors nor PKC inhibitors. Myosin light chain kinase inhibitors inhibited movements of PMNs induced by both GM-CSF and fMLP. These findings also imply that some aspects of the signal transduction pathway of GM-CSF leading to random migration is different from that of fMLP. Our findings suggest that cell movements are controlled through diverse signal transduction systems.
Generation of multinucleated giant cells by culture of monocyte-derived macrophages with IL-4
Authors: Dugast Catherine , Gaudin Annette , Toujas Louis 
Published: January 2018

Abstract
Culturing human monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) has been reported to provoke the formation of multinucleated giant cells (GCs). In the present work, GCs were generated in a two-step procedure in which macrophages were first differentiated from monocytes before being fused into GCs. The two cytokines used acted sequentially. GM-CSF was required for monocyte differentiation and IL-4 for macrophage fusion. Macrophages were purified from cultures of blood mononuclear cells maintained for 7 days in plastic bags. When seeded in conventional plastic-ware in the presence of IL-4, these macrophages showed an increased motility, spread in thin cytoplasmic lamellae, regrouped in clusters, and within 1–3 weeks, differentiated into GCs. Multinucleated cells also appeared in IL-4-untreated macrophage cultures but the number of nuclei did not exceed 2 or 3, compared with more than 30 in the presence of IL-4. Scanning electron microscopy of GCs showed highly developed pseudopods. GCs reacted with anti-CD11b, -CD54, -CD68, -HLA-ABC, and -HLA-DR monoclonal antibodies and AMH-152 but were CD14- and CD64-negative. Both untreated and IL-4-treated macrophages conserved pinocytic and phagocytic activity. Thus, IL-4 induced a differentiation process in which macrophages lost markers like CD14 and CD64, acquired an enhanced membrane motility, and fused in multinucleated GCs.
Mechanisms of neutrophil-induced parenchymal cell injury
Authors: Jaeschke Hartmut , Smith C Wayne 
Published: January 2018

Abstract
Neutrophils are involved in organ damage induced by an excessive acute inflammatory response after ischemia-reperfusion, trauma, and sepsis. In addition to causing vascular injury, neutrophils can transmigrate and attack parenchymal cells. This review summarizes recent advances in our understanding of neutrophil-induced parenchymal cell injury using the liver as an example. Reviewed are the mechanisms of neutrophil sequestration in the hepatic vasculature, transendothelial migration, adherence to hepatic parenchymal cells, and mechanisms of cytotoxicity. Discussed are the involvement of various adhesion molecules in these processes, the role of cytokines and chemokines in the pathophysiology, as well as the effects of proteases and reactive oxygen species released by neutrophils. The emerging understanding of the basic mechanisms of neutrophil-induced organ damage is critical for the development of therapeutic strategies to attenuate excessive acute inflammatory responses without compromising essential host defense mechanisms.
Increased expression of an endopeptidase (γ-EGE/IDE) hydrolyzing β-endorphin during differentiation and maturation of bone marrow macrophages
Authors: Sarada Boppana , Thiele Dwain , Dang Tuyet , Safavi Afshin , Hersh Louis B , Cottam Gene L 
Published: January 2018

Abstract
The presence and regulated expression of peptidase activity is a powerful mechanism with the potential to terminate or alter receptor recognition, cell membrane signal transduction, and physiological responses of immune cells to exogenous opioid peptides. In this study, the expression of an endopeptidase that hydrolyzes β-endorphin to γ-endorphin and other peptide products was investigated during in vitro differentiation and maturation of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) -derived, bone marrow-derived macrophages. In freshly isolated intact isolated mouse bone marrow cells the rate of β-endorphin hydrolysis is undetectable (&lt;0.1 nmol β-endorphin hydrolyzed/h/106 cells). However, total intracellular β-endorphin hydrolytic activity was increased significantly to 20.0 ± 1.7 nmol/ h/106 cells in the mature mouse macrophages derived in vitro by culture with rGM-CSF. rGM-CSF-derived macrophages expressed significantly higher levels of both protein and mRNA for the major β-endorphin endopeptidase, γ-endorphin-generating enzyme/insulin-degrading enzyme (γ-EGE/IDE). Moreover, this enzymatic activity appears to be responsible for cleavage of exogenous β-endorphin by intact rGM-CSF-derived macrophages or peritoneal macrophages to generate γ-endorphin and other peptide products.
Phagocytosis of Gram-negative bacteria by a unique CD14-dependent mechanism
Authors: Schiff Deborah E , Kline Lois , Soldau Katrin , Lee J D , Pugin Jerome , Tobias Peter S , Ulevitch Richard J 
Published: January 2018

Abstract
THP-l-derived cell lines were stably transfected with constructs encoding glycophosphatidylinositol (GPI) -anchored or transmembrane forms of human CD14. CD14 expression was associated with enhanced phagocytosis of serum (heat-inactivated) -opsonized Escherichia coli(opEc). Both the CPI-anchored and transmembrane forms of CD14 supported phagocytosis of opEc equally well. Lipopolysaccharide-binding protein (LBP) played a role in CD14-dependent phagocytosis as evidenced by inhibition of CD14-dependent phagocytosis of opEc with anti-LBP monoclonal antibody (mAb) and by enhanced phagocytosis of E. coliopsonized with purified LBP. CD14-dependent phagocytosis was inhibited by a phosphatidylinositol (PI) 3-kinase inhibitor (wortmannin) and a protein tyrosine kinase inhibitor (tyrphostin 23) but not a protein kinase C inhibitor (bisindolylmaleimide) or a divalent cation chelator (ethylenediaminetetraacetate). Anti-LBP mAb 18G4 and anti-CD 14 mAb 18E12 were used to differentiate between the pathways involved in CD14-dependent phagocytosis and CD14-dependent cell activation. F(ab′)2 fragments of 18G4, a mAb to LBP that does not block cell activation, inhibited ingestion of opEc by THP1-wtCD14 cells. 18E12 (an anti-CD14 mAb that does not block LPS binding to CD14 but does inhibit CD14-dependent cell activation) did not inhibit phagocytosis of LBP-opEc by THP1-wtCD14 cells. Furthermore, CD14-dependent phagocytosis was not inhibited by anti-CD 18 (CR3 and CR4 β-chain) or anti-Fcγ receptor mAb.
Epithelioid cells from foreign-body granuloma selectively express the calcium-binding protein MRP-14, a novel down-regulatory molecule of macrophage activation
Authors: Aguiar-Passeti T , Postal E , Sorg C , Mariano M 
Published: January 2018

Abstract
The S-100 proteins MRP-8 and MRP-14 are expressed by cells of the myelomonocytic lineage, either alone or simultaneously during certain stages of cellular differentiation. We demonstrate that MRP-14 but not MRP-8 was detected by immunostaining in the cytoplasm of epithelioid cells on the surface of round coverslips implanted for 14 days into the subcutaneous tissue of mice. Using this experimental model, our laboratory has previously shown that epithelioid macrophages are poor phagocytic cells that release a macrophage-deactivating factor (MDF) in short-term cultures. The full chemical characterization of MDF has not been achieved so far. We provide evidence that the calcium-binding protein MRP-14 was also released by epithelioid macrophages in short-term cultures and that its neutralization from the culture medium after addition of monoclonal antibody anti-MRP-14 abolished the MDF activity of the conditioned medium. Purified or recombinant human MRP-14 but not MRP-8 inhibits the respiratory burst of BCG-activated macrophages. Recombinant mouse MRP-14 also down-regulate macrophage activation in vitro, and PMA does not revert the inhibitory effect induced by MRP-14. It is thus concluded that epithelioid cells from foreign-body granuloma express and release MRP-14 in short-term cultures and that this molecule is endowed with MDF activity.
Anti-inflammatory activities of cAMP-elevating agents: enhancement of IL-10 synthesis and concurrent suppression of TNF production
Authors: Eigler Andreas , Siegmund Britta , Emmerich Uta , Baumann Klaus H , Hartmann Gunther , Endres Stefan 
Published: January 2018

Abstract
Interleukin-10 (IL-10) and tumor necrosis factor (TNF) exert key roles in some acute and chronic inflammatory diseases. In this study we investigated (1) the potency of different cAMP-elevating agents in enhancing IL-10 synthesis, (2) the involvement of protein kinase A in this enhancement, and (3) the mutual dependence of cAMP-enhanced IL-10 formation and cAMP-suppressed TNF synthesis. Rolipram, a specific phosphodiesterase inhibitor and cicaprost, a prostacyclin analogue, were applied as cAMP-elevating agents. The stable cAMP antagonist (Rp)-cAMPS was used to abrogate activation of protein kinase A. Human peripheral blood mononuclear cells were stimulated with lipopolysaccharide (LPS). TNF was quantified by radioimmunoassay, IL-10 by enzyme-linked immunosorbent assay, and mRNA by reverse transcriptase-polymerase chain reaction. After LPS stimulation alone 253 ± 45 pg/mL IL-10 was synthesized, which increased to 644 ± 117 pg/mL in the presence of 1 μM rolipram. (Rp)-cAMPS reversed this increase of IL-10 formation. In the same samples, the LPS-stimulated production of TNF was markedly attenuated by rolipram or cicaprost. A kinetic analysis revealed a significant increase in TNF production before IL-10 formation was detectable. These results demonstrate that (1) cAMP-elevating agents enhance IL-10 synthesis and suppress TNF production; (2) these regulative functions of cAMP-elevating agents are mediated by activation of protein kinases A; (3) suppression of TNF synthesis by cAMP in the early phase is not mediated by endogenous IL-10. Taken together, rolipram and cicaprost exert a dual regulatory function by enhancing IL-10 formation and attenuating TNF synthesis.
Endotoxin-induced abortion in mice is mediated by activated fetal macrophages
Authors: Wang Yu-Ying , Tawfik Ossama , Wood Gary W 
Published: January 2018

Abstract
Leukocyte numbers and function were assessed in uterus, placenta, and fetus during endotoxin-induced abortion. Tissues initially contained high numbers of macrophages but no granulocytes or lymphocytes. Endotoxin treatment resulted in rapid, transient neutrophil accumulation in uterus and placenta. Moderate increases in macrophage numbers occurred in the uterus but there were no changes in tissue distribution. Myometrial, endothelial, and epithelial cells were unaffected by endotoxin but proliferating, differentiated fibroblasts that made up the primary decidua disappeared. As abortion progressed, the proportional representation of macrophages in placenta and embryo increased until, during the late stages of fetal resorption, they constituted nearly all viable fetal cells. At the same time, overall expression of class II major histocompatibility complex gene products increased in maternal and fetal tissue. Leukocyte distribution and macrophage activation data suggested that endotoxin-induced fetal failure is mediated by products of activated maternal and fetal macrophages acting in concert to destroy actively proliferating maternal and fetal cells.
Activated polymorphonuclear leukocytes affect red blood cell aggregability
Authors: Baskurt Oguz K , Meiselman Herbert J 
Published: January 2018

Abstract
Activated leukocytes can affect adjacent cells by generating oxygen free radicals and secreting proteolytic enzymes, and red blood cells (RBC) exposed to such agents should be susceptible to their effects. This study was thus designed to investigate the effects of activated polymorphonuclear leukocytes (PMN) on RBC aggregability (i.e., on intrinsic RBC aggregation characteristics). PMN were isolated from human blood by density separation and suspended in glucose-enriched buffer with RBC isolated from the same blood sample (RBC/PMN ratio of 150:1). PMN were then activated in this suspension by adding 1 ng/mL tumor necrosis factor α (TNF-α) and 10–7 M N-formyl-methionyl-leucyl-phenylalanine (fMLP) or fMLP alone. After incubation for 2 h at 37°, RBC aggregation behavior in autologous plasma was assessed; RBC deformability and partition coefficients were also measured. RBC aggregation was significantly increased after incubation and deformability and partitioning were decreased; these effects were prevented by phenylmethylsulfonyl fluoride (1 mM) or superoxide dismutase (20 μg/mL) plus catalase (40 μg/mL). TNF-α and fMLP alone had no effect on RBC aggregation if PMN were not present. Activated PMN can thus markedly affect RBC aggregability, apparently via both proteolytic enzymes and oxygen free radicals; enhanced aggregation seen in clinical states associated with PMN activation or observed during in vivo RBC aging may also involve such PMN-RBC interactions.