bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIP-3α induces human eosinophil migration and activation of the mitogen-activated protein kinases (p42/p44 MAPK)
Authors: Sullivan Susan K , McGrath Douglas A , Liao Fang , Boehme Stefen A , Farber Joshua M , Bacon Kevin B 
Published: January 2018

Abstract
The CC chemokine macrophage inflammatory protein-3α (MIP-3α) is the product of recent electronic cloning efforts, however, little characterization of its spectrum of biological effects has been undertaken. Human eosinophils exhibited pertussis-toxin-sensitive migration in response to human recombinant (hr)MIP-3α. Messenger RNA for the MIP-3α receptor, CCR-6, and low levels of surface expression were demonstrated by reverse transcriptase-polymerase chain reaction and FACS analysis. Analyses of cell signaling revealed dose-dependent increases in intracellular calcium mobilization, calcium transients that were, however, greatly reduced when compared with MCP-3-induced responses. Further investigations of MIP-3α-induced signal transduction revealed time- and dose-dependent, partially pertussis toxin-dependent, increases in phosphorylation of the p42/p44 mitogen-activated protein kinases (MAPK) that occurred at 10- to 100-fold lower concentrations, and that were linked to a phosphoinositide 3-kinase pathway. These results suggest that MIP-3α can regulate multiple, parallel signal transduction pathways in eosinophils, and suggest that MAPK activation by MIP-3α in eosinophils is a significant signaling pathway for migration induction. J. Leukoc. Biol. 66: 674–682; 1999.
C/EBP regulates the promoter of the eosinophil-derived neurotoxin/RNS2 gene in human eosinophilic cells
Authors: Baltus Belinda , Buitenhuis Miranda , van Dijk Thamar B , Vinson Charles , Raaijmakers Jan A M , Lammers Jan-Willem J , Koenderman Leo , de Groot Rolf P 
Published: January 2018

Abstract
The eosinophil-derived neurotoxin (EDN), a member of the mammalian ribonuclease family, is found in the large specific granules of human eosinophilic leukocytes. We have investigated the role of the C/EBP transcription factor family in the regulation of EDN promoter activity. Here we show that the C/EBP family is involved in intrinsic regulation of EDN promoter activity. We have identified a C/EBP binding site located at – 124 in the proximal promoter of the EDN gene. Mutation of this C/EBP site results in a decrease of promoter activity in HL-60-eos cells as well as in eosinophils differentiated in vitro from CD34+ cells. Different C/EBP proteins are able to bind to the C/EBP site as shown by gel shift assay. Our results indicate the importance of the C/EBP family in the regulation of the EDN gene in eosinophils. J. Leukoc. Biol. 66: 683–688; 1999.
Migration of leukocytes across endothelium and beyond: molecules involved in the transmigration and fate of monocytes
Authors: Muller William A , Randolph Gwendalyn J 
Published: January 2018

Abstract
Passage of leukocytes across the endothelial lining into sites of inflammation has been shown to be regulated largely by platelet/endothelial cell adhesion molecule-1 (PECAM/CD31). We summarize recent work from our laboratory documenting that PECAM is involved both in diapedesis and the subsequent step of migration across the basal lamina. The former process involves a homophilic interaction between the amino-terminal extracellular domains of PECAM on the leukocyte and on the endothelial cell. The latter process involves a heterophilic interaction between the membrane-proximal extracellular domain of PECAM and an unknown ligand(s) in the subendothelial basal lamina. These findings are demonstrated in both in vitro and in vivo models. For monocytes, however, transmigration is just the first step in the next phase of their lives. In addition to their specific recruitment during the inflammatory response, many monocytes constitutively leave the bloodstream to enter tissues. However, only a fraction of these become tissue macrophages. In an in vitro model of monocyte emigration, approximately half of the leukocytes that initially transmigrate an endothelial monolayer migrate back out in the basal-to-apical direction within the next 2 days. This reverse transmigration cannot be blocked by anti-PECAM reagents, but involves p-glycoprotein and tissue factor expressed on the leukocytes. The reverse transmigrating cells are phenotypically dendritic cells (DC). Their maturation to mature DC can be accelerated by inclusion of inflammatory stimuli in the co-culture. The cells that remain behind in the subendothelial collagen are phenotypically macrophages. We postulate that a major source of DC in lymph nodes is cells derived from monocytes that enter a tissue via the blood and leave several days later via afferent lymphatic channels. J. Leukoc. Biol. 66: 698–704; 1999.
Modular components of phagocytosis
Authors: Greenberg Steven 
Published: January 2018

Abstract
Phagocytosis is an evolutionarily ancient host cell endocytic response to particulate stimuli. Phagocytic leukocytes utilize highly conserved programs of signaling and motility to engulf foreign pathogens. Particle ingestion requires actin assembly and pseudopod extension, two cellular events that coincide spatially and temporally. This review presents evidence that phagocytosis proceeds in discrete but coordinated stages. In the case of receptors for the Fc portion of IgG (FcγRs), engagement of the IgG ligands results in receptor aggregation and recruitment of cytosolic tyrosine kinases, most notably Syk. Phosphorylation of tyrosine residues occurs within immunoreceptor tyrosine activation motif (ITAM) consensus sequences found in FcγR subunits, which leads to further recruitment and activation of Syk via its SH2 domains. Syk tyrosine kinase activity is required for FcγR-mediated actin assembly, which is controlled by several GTPases, including Rac1 and Cdc42. Phagocytosis and Rac-mediated cytoskeletal alterations also require the participation of another low molecular GTPase, ARF6. Simultaneously, phosphati-dylinositol 3-kinase is recruited to the plasma membrane, which triggers exocytosis from an intracellular membrane source that is required for pseudopod extension. The source of this membrane is as yet unknown. This review focuses on individual components of phagocytosis and emphasizes that the signaling requirements for each of these is distinct. J. Leukoc. Biol. 66: 712–717; 1999.
Macrophage scavenger receptors and foam cell formation
Authors: de Villiers Willem J S , Smart Eric J 
Published: January 2018

Abstract
Scavenger receptors bind and internalize modified low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Because the expression of scavenger receptors is not down-regulated by cholesterol, macrophages (M) expressing scavenger receptors can internalize substantial quantities of cholesteryl ester from oxidized LDL and HDL, leading to foam cell formation. M express several different classes of the growing scavenger receptor family on their cell surface and their relative contribution to M cholesterol physiology and atherogenesis is the subject of intense investigation. We focus on the potential role of two scavenger receptors, macrosialin and SR-BI/II in M cholesterol metabolism. Macrosialin is a predominantly M-specific oxidized LDL-binding protein and an atherogenic diet markedly up-regulates its hepatic expression in atherosclerosis-susceptible and atherosclerosis-resistant mouse strains. The HDL receptor, SR-BI and its splicing variant SR-BII, colocalize with caveolin in caveolae in M. Caveolae are initial acceptor sites for cholesteryl esters and these findings indicate a possible role for caveolae and SR-BI in M-selective lipid uptake and in regulating M cholesterol flux in the vascular wall. J. Leukoc. Biol. 66: 740–746; 1999.
Intracellular niches for extracellular bacteria: lessons from Helicobacter pylori
Authors: Allen Lee-Ann H 
Published: January 2018

Abstract
Helicobacter pylori colonizes the gastric epithelium of humans and plays a causative role in peptic ulcer disease and perhaps gastric cancer. H. pylori proliferates in the mucus layer over the epithelium and is not cleared by the host immune response. Although the mucus layer is the major reservoir of H. pylori in vivo, a growing body of evidence suggests that H. pylori can persist in multiple intracellular locales. Clinical isolates of H. pylori invade epithelial monolayers at least as well as Shigella. The intracellular organisms are cytotoxic, and bacterial microcolonies form on the exposed basement membrane. Both mononuclear phagocytes and neutrophils phagocytose unopsonized H. pylori. However, the internalized organisms are not killed efficiently and our recent data suggest that H. pylori disrupts phagosome maturation. Collectively, the data support the hypothesis that intracellular H. pylori represent a reservoir of organisms that contributes to bacterial persistence, host tissue damage, and treatment failure. J. Leukoc. Biol. 66: 753–756; 1999.
Interleukin-1 production by mouse macrophages is regulated in a feedback fashion by nitric oxide
Authors: Obermeier Florian , Gross Volker , Schölmerich Jürgen , Falk Werner 
Published: January 2018

Abstract
The pleiotropic cytokine interleukin-1 (IL-1) is an inducer of the inducible nitric oxide synthase (iNOS). It was surprising to find that treatment of normal mice with an iNOS inhibitor resulted in detectable IL-1β mRNA in colon and spleen, suggesting feedback regulation. When mouse peritoneal exudate cells (PEC) or RAW 264.7 cells were stimulated with lipopolysaccharide (LPS), concomitant inhibition of iNOS resulted in an increase of IL-1β and IL-1α protein secretion. Conversely, after addition of the NO-generating compound NOC-18, IL-1β and IL-1α concentrations in supernatants were dose-dependently reduced. Co-stimulation with interferon-γ (IFN-γ) reversed the NOC-18-mediated suppression of IL-1α protein concentration into an almost fivefold increase in RAW 264.7 cells. This effect was specific for IL-1α and was also seen in PEC. The mRNA expression for IL-1β and IL-1α in RAW 264.7 cells correlated with the protein levels, suggesting transcriptional regulation by NO. Dysregulated IL-1/NO cross-regulation may play a role in inflammatory diseases. J. Leukoc. Biol. 66: 829–836; 1999.
Macrophage responses to hypoxia: relevance to disease mechanisms
Authors: Lewis J S , Lee J A , Underwood J C E , Harris A L , Lewis C E 
Published: January 2018

Abstract
Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset and progression of many pathological states. The mechanisms underlying this response are well described in such conditions as wound healing and malignant tumors, where tissue-specific signals enhance the extravasation of blood monocytes and their subsequent differentiation into macrophages. Recent evidence suggests that macrophages may also be stimulated by microenvironmental factors present in diseased tissues to perform distinct, tissue-specific activities. One such factor, hypoxia (low oxygen tension), results from insufficient vascular perfusion of a given tissue. Various studies have shown that experimental hypoxia alters the morphology, expression of cell surface markers, viability, phagocytosis, metabolic activity, and release of cytokines by macrophages. Here we review the evidence for these macrophage responses to hypoxia, the involvement of co-stimuli, and their implications for the role of macrophages in various disease processes. Because the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discuss their possible involvement in the effects of hypoxia on gene expression in macrophages. J. Leukoc. Biol. 66: 889–900; 1999.
Functional expression of CD43 on human natural killer cells
Authors: Aguado Enrique , Santamaría Manuel , Gallego María Dolores , Peña José , Molina Ignacio J 
Published: January 2018

Abstract
CD43 is the major leukocyte sialoglycoprotein that plays important functional roles in neutrophils and lymphocytes. However, the expression of CD43 on human natural killer (NK) cells and its participation in the regulation of NK activity has not been studied. We have therefore investigated the expression of CD43 isoforms on human NK cell subpopulations as well as the role of this molecule in NK cell activation and cytotoxicity. We found that CD56bright and CD56dim NK cells express different sialylated forms of CD43, observing that activation of the CD56bright NK cells induces the change of tetrasaccharide O-glycans to hexasaccha-ride O-glycans on CD43. Cross-linking of the molecule with mAbs results in a metalloprotease-dependent loss of CD43 from the NK cell surface, whereas soluble anti-CD43 mAbs induce a vigorous NK cell proliferation. This property is distinct from T cells, which proliferate after CD43 cross-linking only in the presence of monocytes. Occupancy of the CD43 receptor on NK cells transduces specific signals, leading to enhanced killing activity and tyrosine phosphorylation and de-phosphorylation of several substrates. We therefore propose that CD43 significantly contributes to the regulation of the NK cell function by participating in the control of effector/target interactions and, if pertinent, by transducing activation signals. J. Leukoc. Biol. 66: 923–929; 1999.
Human polymorphonuclear neutrophils express a B7-1-like molecule
Authors: Windhagen Anja , Maniak Susanna , Gebert Andreas , Ferger Isabel , Wurster Ulrich , Heidenreich Fedor 
Published: January 2018

Abstract
Polymorphonuclear neutrophils (PMN) are part of the innate immune system and are first-line effector cells in acute inflammatory responses. On activation PMNs secrete cytokines and oxygen metabolites that might be involved in the regulation of the acquired immune response. We show here that peripheral blood PMNs constitutively express a B7-1-like molecule as detected by immunostaining with several B7-1 antibodies. Reverse transcriptase-polymerase chain reaction using three sets of primers spanning different regions of B7-1 indicate dissimilarities at the mRNA level. B7-1 mRNA is expressed in bone marrow cells and lipopolysaccharide (LPS)-stimulated but not in unstimulated PMNs. The B7-1-like molecule is localized to the cytoplasmic granules and translocated to the cell surface after stimulation with LPS or interleukin-12 in some donors. Binding of CTLA4-Ig suggests that the B7-1-like molecule can interact with functional B7 ligand and might be important in the immunobiology of PMNs. J. Leukoc. Biol. 66: 945–952; 1999.
Characterization of a CSF-induced proliferating subpopulation of human peripheral blood monocytes by surface marker expression and cytokine production
Authors: Finnin Maribel , Hamilton John A , Moss Suzanne T 
Published: January 2018

Abstract
The phenotype of a subpopulation(s) of human monocytes which has been shown to proliferate in vitro in response to macrophage colony-stimulating factor (M-CSF or CSF-1) and granulocyte-macrophage CSF (GM-CSF) is as yet unknown. To identify this proliferating subpopulation(s) we demonstrated first that DNA synthesis was occurring under culture conditions suitable for flow cytometric evaluation. Flow cytometric analysis of surface antigen expression identified that after 5 days of culture the proliferating subpopulation of monocytes expressed CD14, CD13, CD33, CD11b, CD11c, CD87, HLA-DR, CD45RO, and did not express CD86, CD34, CD80, CD4, CD16, and CD56. In addition, these proliferating monocytes (representing approximately 5% of total monocytes) were shown to produce the proinflammatory cytokines interleukin-6 and tumor necrosis factor α in response to lipopolysaccharide stimulation. Further characterization and subsequent isolation of this subpopulation of monocytes may provide new and important information necessary to understand inflammatory diseases such as rheumatoid arthritis, where local proliferation at the site of inflammation may be a key factor contributing to the chronicity of the disease. J. Leukoc. Biol. 66: 953–960; 1999.
Synergistic action of pro-inflammatory agents: cellular and molecular aspects
Authors: Paludan Søren R 
Published: January 2018

Abstract
Generation of an inflammatory response is a complex process involving multiple factors acting in parallel and in concert. Viruses, parasites, and bacteria, particularly lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, act cooperatively with the cytokine interferon (IFN)-γ to induce many of the genes involved in inflammation. In addition, these components synergistically induce secretion of tumor necrosis factor α (TNF-α), which also synergizes strongly with IFN-γ. The molecular mechanisms underlying the synergistic gene induction discussed in this review involve cooperative activation of transcription factors. IFN-γ-activated signal transducer and activator of transcription 1 and interferon regulatory factor-1 function synergistically with nuclear factor κB activated by LPS and TNF-α. In addition, cross-talk between the signal transduction pathways upstream of the activation of the transcription factors contributes to generation of the synergistic action. Cooperative activity of proinflammatory agents profoundly influences the immune response to infections and the efficiency of cellular clearance mechanisms. J. Leukoc. Biol. 67: 18–25; 2000.
CD40-CD40 ligand
Authors: van Kooten Cees , Banchereau Jacques 
Published: January 2018

Abstract
CD40 is a cell surface receptor that belongs to the tumor necrosis factor-R (TNF-R) family, and that was first identified and functionally characterized on B lymphocytes. Its critical role in T cell-dependent humoral immune responses was demonstrated by patients with the hyper-IgM syndrome, as well as by gene targeting in mice. However, in recent years it has become clear that CD40 is expressed much more broadly, including expression on monocytes, dendritic cells, endothelial cells, and epithelial cells. In addition, the CD40-ligand (CD40-L/CD154), a member of the TNF family, is also expressed more widely than activated CD4+ T cells only. Therefore it is now thought that CD40-CD40-L interactions play a more general role in immune regulation. Collectively these studies have culminated in pre-clinical and clinical studies that are in progress. This article reviews recent developments in this field of research, with main emphasis on (1) structure and expression of CD40 and its ligand; (2) CD40 signal transduction; (3) in vitro function of CD40 on different cell types; and (4) in vivo functions of CD40/CD40-L interactions. J. Leukoc. Biol. 67: 2–17; 2000.
Antimicrobial effects of α-MSH peptides
Authors: Cutuli Mariagrazia , Cristiani Silvia , Lipton James M , Catania Anna 
Published: January 2018

Abstract
The presence of the ancient antiinflammatory peptide α-melanocyte-stimulating hormone [α-MSH (1–13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. α-MSH and and its carboxy-terminal tripeptide (11–13, KPV) were determined to have antimicrobial influences against two major and representative pathogens: Staphylococcus aureus and Candida albicans. α-MSH peptides significantly inhibited S. aureus colony formation and reversed the enhancing effect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentrations including the physiological (picomolar) range. Small concentrations of α-MSH peptides likewise reduced viability and germ tube formation of the yeast C. albicans. Antimicrobial influences of α-MSH peptides could be mediated by their capacity to increase cellular cAMP. Indeed, this messenger was significantly augmented in peptide-treated yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo) partly reversed the killing activity of α-MSH peptides. Reduced killing of pathogens is a detrimental consequence of therapy with anti-inflammatory drugs. Because α-MSH has potent anti-inflammatory effects we determined influences of α-MSH on C. albicans and S. aureus killing by human neutrophils. α-MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. α-MSH peptides that combine antipyretic, antiinflammatory, and antimicrobial effects could be useful in treatment of disorders in which infection and inflammation coexist. J. Leukoc. Biol. 67:233–239; 2000.
Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase
Authors: Karlsson Anna , Nixon Jennifer B , McPhail Linda C 
Published: January 2018

Abstract
The neutrophil NADPH-oxidase can be activated by protein kinase C (PKC) agonists such as phorbol myristate acetate (PMA), resulting in superoxide anion release. This superoxide release is independent of phosphatidylinositol 3-kinase (PI 3-kinase) because the inhibitor wortmannin does not affect the response. In this study, PMA is shown to also induce a wortmannin-sensitive NADPH-oxidase activation, however, not resulting in release of superoxide but in intracellular production of the radical. This indicates that two pools of NADPH-oxidase, one localized in the plasma membrane and the other in the granule membranes, are separately regulated and the signal transduction pathways leading to activation of these pools differ regarding involvement of PI 3-kinase. Activation of both pools was dependent on ERK/MAPK kinase (MEK) activity and protein phosphatase 1 and/or 2A. As the two oxidase responses were differently affected by the inhibitor Gö-6850, different PKC isozymes are suggested to take part in the two signal transduction pathways. J. Leukoc. Biol. 67: 396–404; 2000.
Phosphatidylinositol 3-kinase and mTOR mediate lipopolysaccharide-stimulated nitric oxide production in macrophages via interferon-β
Authors: Weinstein Steven L , Finn Alexander J , Davé Shaival H , Meng Fanying , Lowell Clifford A , Sanghera Jasbinder S , DeFranco Anthony L 
Published: January 2018

Abstract
Bacterial lipopolysaccharide (LPS) elicits responses by macrophages that help the body repel infections. Recent evidence indicates that phosphatidylinositol 3-kinase (PI 3-kinase) may mediate some of these responses. Here, we show that exposing macrophages to LPS rapidly increased membrane-associated PI 3-kinase activity and also elevated p70 S6 kinase activity. Inhibitors of PI 3-kinase or the mammalian target of rapamycin (mTOR) fully blocked p70 S6 kinase activation, implying that this kinase is controlled by PI 3-kinase and mTOR. These inhibitors also substantially reduced LPS-induced nitric oxide (NO) production. This inhibition was, in part, attributable to impaired LPS-stimulated secretion of interferon-β, an autocrine co-factor for NO production. However, the addition of exogenous interferon-β did not fully restore NO production, indicating that the NO response was being inhibited by another mechanism as well. Together, these data suggest that PI 3-kinase, mTOR, and possibly p70 S6 kinase mediate LPS-induced NO production by regulating the secretion of interferon-β and by a second undefined mechanism. J. Leukoc. Biol. 67: 405–414; 2000.