bluuebunny/crossref_metadata_2025_split huggingface dataset:
The EGF-TM7 family: unusual structures at the leukocyte surface
Authors: McKnight Andrew J , Gordon Siamon 
Published: January 2018

Abstract
The isolation of cDNA clones encoding mouse F4/80, human epidermal growth factor (EGF) module-containing mucin-like hormone receptor 1 (EMR1) and human CD97 has resulted in the description of a novel family of seven-transmembrane spanning cell surface molecules. These members of the EGF-TM7 family are characterized by a variable number of NH2-terminal EGF domains and seven transmembrane-spanning hydrophobic regions, which demonstrate a degree of sequence homology to the corresponding region in members of the G-protein-coupled peptide hormone receptor family. The F4/80 molecule is macrophage-restricted, as determined by immunohistochemical analysis of a wide range mouse tissues, while mRNA transcripts encoding EMR1, the predicted human F4/80 homologue, also appear to be abundantly expressed by cells of the myelomonocytic lineage. CD97, for which a cellular ligand has been identified (CD55), is expressed on a diverse array of leukocytes and is markedly upregulated on activated T and B cells. The regulation of expression of the EGF-TM7 genes, the physiologic function(s) of these novel receptors and the further identification of their ligands is the subject of both intense study and this review.
CD40L-CD40 interactions regulate endothelial cell surface tissue factor and thrombomodulin expression
Authors: Miller Debra L , Yaron Renat , Yellin Michael J 
Published: January 2018

Abstract
During immune responses, activated endothelial cells down-regulate thrombomodulin and up-regulate tissue factor expression leading to the development of a procoagulant surface. CD4+ T cells are known to promote endothelial cell procoagulant activity, however, the molecular interactions that mediate this effect are not completely known. CD40L is an activation-induced CD4+ T cell surface molecule that functionally interacts with CD40 expressed on endothelial cells. In this study we ask if CD40L-CD40 interactions modulate endothelial cell surface tissue factor or thrombomodulin expression in vitro. Human umbilical vein endothelial cells (HUVEC) were cocultured with control cells or CD40L+ Jurkat T cells in the presence or absence of anti-CD40L mAb. By two-color FACS analysis we demonstrated that CD40 ligation induces HUVEC tissue factor expression and thrombomodulin down-regulation. Utilizing neutralizing antibodies, we show that CD40L-mediated tissue factor and thrombomodulin modulation, as well as E-selectin and VCAM-1 up-regulation, is independent of tumor necrosis factor α, interleukin-1α, or interleukin-1β production. Together these data suggest that CD40L-CD40 interactions may directly regulate endothelial cell procoagulant activity during inflammatory responses.
Processing of C5a by human polymorphonuclear leukocytes
Authors: Hetland Geir , Pfeifer Philippe H , Hugli Tony E 
Published: January 2018

Abstract
Uptake of human C5a by neutrophils was monitored in vitro using both 125I-labeled and unlabeled C5a. The ligand was internalized by the cells in a dose-dependent manner and maximal binding/uptake was observed after 5 min of incubation. Neutrophils were incubated with labeled C5a and the cytosol and supernatant were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. C5a degradation products were primarily observed in the supernatant, whereas most of the protein remained intact in the cytosol even after 60 min of incubation. Cytosol from neutrophils incubated for 20 min with unlabeled C5a was examined by radioimmunoassay and found to contain antigenically intact C5a and retained the ability to induce a neutrophil (shape change) response. The functional activity of C5a recovered from the cytosol was inhibited by antibodies to either C5a or the C5a receptor (CD88). This data supports our hypothesis that although C5a is internalized it remains antigenically intact and functionally active inside the cell and is primarily degraded extracellularly.
Role of the liver in T cell differentiation—generation of CD3–CD4+/CD8+TCRβ– cells and CD3–4–8–TCRβ+ cells from CD4–8–TCRβ– athymic nude bone marrow cells by culture with parenchymal liver cells
Authors: Mabuchi Ayako , Kodaira Yuzo , Norose Yoshihiko , Saizawa Mitsuyoshi , Kitajima Masumi , Yokomuro Kozo 
Published: January 2018

Abstract
To investigate the influence of the liver on differentiation of hematopoietic stem cells/ pro-T cells, TN-NWP-BMC (athymic nude bone marrow cells that were treated with anti-TCRβ, anti-CD4, and anti-CD8 Abs plus complement and then passed through a nylon wool column) were cultured on parenchymal liver cells. After culture for 2.5 days, CD3–4–8–TCRβ+ cells and CD3–CD4+/CD8+TCRβ– cells were developed from TN-NWP-BMC. TCRVβ8+ cells comprised 19.9% of CD3–4–8–TCRβ+ cells, and Vβ8 mRNA was detected in the CD3–4–8–TCRβ+ cells by reverse transcriptase-polymerase chain reaction. The CD3–CD4+/CD8+ TCRβ– cells contained not only single-positive cells but also CD4+8+ double-positive cells. The CD8 protein consisted of 88.9% CD8α+β–, 10.1% CD8α+β+, and 1% CD8α–β+ molecules. From these results and the finding of co-expressed antigens, CD3–4–8–TCRβ+ cells and CD3–CD4+/CD8+TCRβ– cells appear to be immature cells not committed to a certain cell lineage.
Construction and expression of a soluble form of human CD30 ligand with functional activity
Authors: Powell Isabelle F , Li Tianhong , Jäck Hans-Martin , Ellis Thomas M 
Published: January 2018

Abstract
CD30 engagement in human lymphoid cells induces pleiotropic cellular responses that affect cellular viability and proliferation, cytokine production, and nuclear factor κB (NF-κB) nuclear translocation. Studies examining the molecular basis for this pleiotropism thus far have relied on the use of antibodies and cells transfected with CD30L to trigger CD30, two methods of receptor induction that present important limitations: antibodies are not physiological receptor-triggering molecules and CD30L transfectants induce high background intracellular signaling in the cells under study. We have generated and expressed a functional soluble human CD30L molecule (sCD30L/CD8α) comprised of the extracellular domain of human CD30L fused to the extracellular domain of the human CD8α chain. Immunoprecipitation and Western blot analysis of sCD30L/CD8α revealed the existence of at least two forms of sCD30L/CD8α, which exhibited molecular sizes consistent with the existence of monomeric and trimeric forms of the molecule. Binding analyses performed using a soluble CD30 fusion protein (sCD30/γ1) confirmed the ability of sCD30L/CD8α to bind to CD30. Functionally, immobilized sCD30L/CD8α-induced cell death in the CD30-expressing lines Karpas-299 and HDLM-2 and reduced proliferative levels in Karpas-299; these effects were inhibitable by the addition of sCD30/γ1. These studies demonstrate the utility of sCD30L/CD8α in characterizing the normal function of CD30L and CD30 and indicate the natural ability of soluble forms of CD30L to trimerize.
IL-10 suppresses LPS-induced KC mRNA expression via a translation-dependent decrease in mRNA stability
Authors: Kim Hee Sun , Armstrong David , Hamilton Thomas A , Tebo Julie M 
Published: January 2018

Abstract
This study examines the mechanism of interleukin-10 (IL-10)-mediated suppression of KC chemokine gene expression in mouse macrophages. Suppression of KC mRNA levels by IL-10 occurred late in the time course of response to lipopolysaccharide (LPS). Equivalent IL-10-mediated suppression was observed when the agent was added 1 h before, simultaneous with, or 1 h after LPS. IL-10 did not inhibit KC gene transcription but rather produced a decrease in the stability of KC mRNA. The suppressive action of IL-10 was prevented in macrophages that were also treated with inhibitors of protein synthesis even when added 2 h after LPS and IL-10. These results suggest that IL-10 acts to destabilize LPS-induced KC mRNA through a process that depends on coincident KC mRNA translation. J. Leukoc. Biol. 64: 33–39; 1998.
Profile of human macrophage transcripts: insights into macrophage biology and identification of novel chemokines
Authors: Chantry David , DeMaggio Anthony J , Brammer Heather , Raport Carol J , Wood Christi L , Schweickart Vicki L , Epp Angela , Smith Aaron , Stine Johnny T , Walton Kim , Tjoelker Larry , Godiska Ronald , Gray Patrick W 
Published: January 2018

Abstract
High throughput partial sequencing of randomly selected cDNA clones has proven to be a powerful tool for examining the relative abundance of mRNAs and for the identification of novel gene products. Because of the important role played by macrophages in immune and inflammatory responses, we sequenced over 3000 randomly selected cDNA clones from a human macrophage library. These sequences represent a molecular inventory of mRNAs from macrophages and provide a catalog of highly expressed transcripts. Two of the most abundant clones encode recently identified CC chemokines. Macrophage-derived chemokine (MDC) plays a complex role in immunoregulation and is a potent chemoattractant for dendritic cells, T cells, and natural killer cells. The chemokine receptor CCR4 binds MDC with high affinity and also responds by calcium flux and chemotaxis. CCR4 has been shown to be expressed by Th2 type T cells. Recent studies also implicate MDC as a major component of the host defense against human immunodeficiency virus. J. Leukoc. Biol. 64: 49–54; 1998.
Ex vivo expansion of hematopoietic cells from umbilical cord blood for clinical transplantation
Authors: Conrad Patricia D , Emerson Stephen G 
Published: January 2018

Abstract
Stem cell transplantation (SCT) has achieved significant therapeutic success over the last 10 years, providing a viable treatment option for many previously incurable diseases. However, several inherent limitations of the procedure have restricted its widespread use. These include: lack of sufficient donors for all recipients, a period of bone marrow (BM) aplasia leading to severe, prolonged neutropenia and thrombocytopenia, and the potential for tumor contamination in autologous SCT. Umbilical cord blood (UCB) provides a unique, and potentially more successful, approach to alleviating these limitations. Ex vivo manipulation of hematopoietic stem (HSCs) and progenitor cells (HPCs) derived from UCB using a liquid culture system has revealed that the primitive HSCs from UCB are not identical to their BM counterparts. In fact, these cells may derive from a more primitive stem cell compartment. Ultimately, successful engraftment of UCB HSCs manipulated in an ex vivo environment may lead to a larger number of these life-saving procedures being performed and the full potential of SCT realized. J. Leukoc. Biol. 64: 147–155; 1998.
Gangliosides of monocyte-derived macrophages of adults with advanced HIV infection show reduced surface accessibility
Authors: Berenson Charles S , Gallery Melissa A , Katari Manpreet S , Foster Edward W , Pattoli Mark A 
Published: January 2018

Abstract
Gangliosides of macrophages are potent immunoregulatory molecules. A monoclonal antibody directed at human macrophage gangliosides (25F4) inhibits macrophage migration with relative specificity. Recent reports suggested that greater expression of Gm1 in mononuclear cells accompanies advanced HIV infection, although others failed to demonstrate any differences in vitro. We purified gangliosides from blood monocyte-derived macrophages obtained from HIV-infected adults. Densitometric analysis of chromatograms demonstrated no differences in relative quantities of any macrophage gangliosides among all HIV-positive and -negative donors. Antibody 25F4 showed equivalent ELISA reactivity with purified macrophage gangliosides of HIV-positive and -negative donors. However, intact macrophages of HIV donors with CD4+ cell counts &lt;200/mm3 showed impaired immunofluorescent surface expression of the 25F4 epitope and concomitant loss of migration inhibitory responsiveness. Thus, although relative content is unchanged, macrophage gangliosides become surface-inaccessible in adults with advanced HIV infection. Our data provide further evidence that dysregulation of glycosphingolipid metabolism in HIV-1 infection contributes to immune dysfunction. J. Leukoc. Biol. 64: 311–321; 1998.
Fas ligand (gld)- and Fas (lpr)-deficient mice do not show alterations in the extravasation or apoptosis of inflammatory neutrophils
Authors: Fecho Karamarie , Cohen Philip L 
Published: January 2018

Abstract
Apoptosis of neutrophils plays a critical role in the resolution of acute inflammation. Neutrophils from human peripheral blood express Fas (CD95) and are sensitive to Fas ligand (FasL)/Fas-mediated apoptosis. Mice carrying spontaneous mutations in the genes for fas ligand (B6/gld) or fas (B6/lpr) were used to assess the role of FasL/Fas in the kinetics and magnitude of neutrophil extravasation to the thioglycolate (TG)-inflamed peritoneum and in the spontaneous apoptosis of TG-elicited neutrophils. The results showed that TG-elicited neutrophils (defined by flow cytometry as GR-1/Ly-6Ghi cells) from normal (B6) and B6/gld mice, but not from the Fas-deficient B6/lpr mice, express high levels of Fas. The TG-elicited neutrophil response began at 2 h, peaked at 4 h, and subsided by 24–48 h after TG administration in all three strains. However, the response was more prolonged in B6 mice, such that B6/gld and B6/lpr mice had fewer neutrophils at 6 h after TG administration than did B6 mice. Further studies showed that 4 h TG-elicited neutrophils from B6, B6/gld and B6/lpr mice undergo apoptosis in vitro at similar rates (as assessed through flow cytometry by the decrease in forward angle light-scatter and externalization of phosphatidylserine (PS; as detected by Annexin V-FITC) that occur as neutrophils undergo apoptosis). Fas expression was down-regulated on apoptotic neutrophils in conjunction with maximal PS externalization and decreased forward angle light-scatter. Collectively, these findings suggest that FasL/Fas-mediated apoptosis is not essential in regulating the lifespan of neutrophils during an acute inflammatory response. The abbreviated inflammatory response observed in FasL/Fas-deficient mice is likely to be a secondary effect of the gld/lpr autoimmune/lymphoproliferative syndrome, and not a direct effect of FasL/Fas on the ability of inflammatory neutrophils to undergo apoptosis. J. Leukoc. Biol. 64: 373–383; 1998.
Nitric oxide enhances the growth of U937 human leukemic cells through a cyclooxygenase-mediated pathway
Authors: Jea Jing-Chi , Liu Tsuei-Chu , Wang Sheng-Yuan , Sung Yen-Jen 
Published: January 2018

Abstract
The mechanisms of exogenous nitric oxide (NO)-enhanced growth of the U937 human myeloid leukemic cells were examined using sodium nitroprusside (SNP) as a NO donor. Treatment with 0.1 mM SNP for 72 h caused a 45 ± 2% increase in U937 cell growth with significantly increased S/G2 + M-phase and decreased G0/G1-phase of the cell cycle. The growth-enhancing effect of SNP was blocked by indomethacin, a cyclooxygenase inhibitor, but not by H7, a broad spectrum kinase inhibitor, or PD98059, a mitogen-activated protein kinase inhibitor. SNP treatment resulted in a dose-dependent increase in prostaglandin E2 (PGE2) production. Furthermore, the addition of exogenous PGE2 not only enhanced U937 cell growth but restored the indomethacin-inhibited mitogenic effect of SNP. We suggest that NO can enhance cell growth through activating the cyclooxygenase pathway and that PGE2 may be an effector molecule for NO-regulated cell proliferation. Our data provide a mechanistic insight into the regulatory role of NO in myelopoiesis. J. Leukoc. Biol. 64: 451–458; 1998.
Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment
Authors: Roos Anja , Schilder-Tol Esther J M , Weening Jan J , Aten Jan 
Published: January 2018

Abstract
CD134 (OX40) is involved in T cell costimulation and T cell-dependent antibody production. We show strongly increased T cell expression of CD134 in a model of T helper 2-mediated systemic autoimmunity, induced by HgCl2. Regulation of CD134 expression on CD4+ T cells was further studied in vitro, identifying CD134 as an early marker of T cell activation. CD134 expression could be induced by interleukin-4, but not by interferon-γ or tumor necrosis factor-α. Effects of interleukin-4 and of phorbol 12-myristate 13-acetate on CD134 expression could be blocked by the protein kinase inhibitor staurosporin. Combination of these stimuli with ionomycin resulted in a strongly synergistic increase of CD134 expression, which was blocked by the calcineurin-inhibitor cyclosporin A. The results demonstrate the involvement of two synergistically acting pathways in induction of CD134 expression. Furthermore, they suggest a role for interleukin-4 in induction of CD134 expression in vivo. J. Leukoc. Biol. 64: 503–510; 1998.
Pathways for eosinophil lipid body induction: differing signal transduction in cells from normal and hypereosinophilic subjects
Authors: Bozza Patricia T , Yu Wengui , Cassara Jessica , Weller Peter F 
Published: January 2018

Abstract
Although lipid bodies, inducible cytoplasmic inclusions active in arachidonic acid metabolism, are abundant in activated leukocytes, including eosinophils, mechanisms for eosinophil lipid body formation are not certain. Eosinophils from hypereosinophilic syndrome (HES) donors contained about twice (~18/cell) as many lipid bodies as eosinophils from normal donors (~10/cell). By immunocytochemistry both 5- and 15-lipoxygenases were localized at lipid bodies in HES eosinophils. Platelet-activating factor (PAF) induced rapid, receptor-mediated increases in lipid bodies in normal and HES eosinophils. Protein kinase C (PKC) inhibitors, chelerythrine and calphostin C, inhibited PAF-induced lipid body formation partially in normal and HES eosinophils. In HES, but not normal, eosinophils, PAF-induced lipid body formation was completely blocked by two tyrosine kinase inhibitors, herbimycin A and genistein, which were not acting on 5-lipoxygenase because they also blocked 5-HETE-induced lipid body formation in HES, and not normal, eosinophils. After 24 h culture with eosinophil growth factor cytokines [interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM-CSF alone but not IL-5 or IL-3 alone], normal eosinophils were induced to exhibit an HES-like phenotype, including increased lipid body numbers and tyrosine kinase-dependent signaling for PAF-induced lipid body formation. Thus, signal transduction mechanisms involved in PAF-induced lipid body formation in eosinophils can be differentially recruited. Tyrosine kinase-dependent signaling is not involved in normal eosinophils, but is active in HES eosinophils and in normal eosinophils cultured with GM-CSF. PKC- and tyrosine kinase-dependent pathways are involved in the formation of eosinophil lipid bodies, which may facilitate enhanced synthesis of lipoxygenase-derived eicosanoids. J. Leukoc. Biol. 64: 563–569; 1998.
Regulation of macrophage phagocytosis of apoptotic neutrophils by adhesion to fibronectin.
Authors: McCutcheon Judith C , Hart Simon P , Canning Mary , Ross Katherine , Humphries Martin J , Dransfield Ian 
Published: January 2018

Abstract
The potential for leukocyte-mediated host tissue damage during resolution of inflammatory responses is influenced by the rate at which extravasated apoptotic leukocytes are cleared from inflammatory sites. Regulation of macrophage capacity for clearance of apoptotic granulocytes is likely to be an important factor determining whether inflammation ultimately resolves or progresses to a chronic state. In this study we have investigated the molecular basis for rapid augmentation of macrophage phagocytosis of apoptotic neutrophils, which was observed following macrophage adhesion to fibronectin. We used a combination of monoclonal antibodies, blocking peptides, and recombinant fibronectin fragments to investigate the role of β1 integrins in mediating the fibronectin effects. Blockade of α5β1 or α4β1 alone did not attenuate fibronectin-augmentation of phagocytosis. In addition, adhesion of macrophages to recombinant fibronectins lacking α4β1 recognition motifs failed to promote phagocytosis of apoptotic neutrophils. Our results would be consistent with a model in which multiple fibronectin receptors, including β1 integrins, act cooperatively to augment macrophage phagocytic responses. Together, these data suggest that the extracellular matrix environment of macrophages may provide regulatory signals that act indirectly to rapidly alter the potential for removal of apoptotic cells and influence the process of resolution of inflammation. J. Leukoc. Biol. 64: 600–607; 1998.
Membrane depolarization and depletion of intracellular calcium stores are associated with delay of apoptosis in human neutrophils
Authors: Chacon-Cruz Enrique , Oelberg David G , Davis Paris , Buescher E Stephen 
Published: January 2018

Abstract
Apoptosis occurs rapidly in human polymorphonuclear leukocytes (PMN) after exposure to 1 mM cycloheximide (CHX). We examined whether this form of stimulated apoptosis altered either resting cytosolic free Ca2+ concentrations ([free Ca]) or membrane potential (Ψ) in PMN and found no significant effects. However, manipulation of either PMN intracellular Ca2+ stores or Ψ was found to delay CHX-induced apoptosis. Depletion of PMN intracellular Ca2+ stores with thapsigargin caused membrane depolarization and significantly delayed CHX-induced apoptosis based on both morphological and annexin-V-fluorescein isothiocyanate binding criteria. Short-term suspension (4 h) of PMN in Ca2+-free buffer depleted internal Ca2+ stores, induced membrane depolarization at 2.5 h, and delayed spontaneous (24 h) apoptosis but had no effect on CHX-induced apoptosis. Rapid membrane depolarization with 150 mM KCl buffer significantly delayed CHX-induced apoptosis, suggesting that depolarization rather than Ca2+ stores depletion was the crucial event. Timing experiments revealed that depolarization within 12 min of CHX exposure significantly delayed apoptosis. Collectively, these observations suggest an early Ψ-sensitive step in the apoptosis pathway initiated by CHX. CHX exposure alone does not alter either resting PMN [free Ca] or Ψ; accompanying depolarization of plasma membrane (either electrochemically or via depletion of internal Ca2+ stores) delays CHX-induced apoptosis in a time-dependent manner. J. Leukoc. Biol. 64: 759–766; 1998.