bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of β1 integrin-dependent adherence of granulocytic HL60 to fibronectin
Authors: Bohnsack John F , Chang Jukay , Zhou Xiaoning , Yednock Ted A 
Published: January 2018

Abstract
We investigated the mechanism of β 1 integrin-mediated adherence of stimulated granulocytic HL60 cells to fibronectin using a monoclonal antibody (15/7) that recognizes β 1 integrins only when the recep tors are active for ligand binding. Phorbol myristate ace tate (PMA) stimulated expression of the 15/7 epitope on granulocytic HL60 by nearly fivefold but had an in significant effect on the expression of the epitope on undifferentiated HL60 cells. These results paralleled the effect of PMA on HL60 and granulocytic HL60 adhesion to fibronectin, indicating that activation of β 1 integrins is important for β 1-mediated adherence of granulocytic HL60 cells to fibronectin. Agonists that stimulate α 5 β 1-dependent human polymorphonuclear leukocyte (PMN) adhesion to fibronectin (C5a and PMA) also up-regulated the 15/7 epitope on purified human PMNs. Although PMA rapidly induces increased levels of filamentous actin (F-actin) in granulocytic HL60 cells and a decrease in F-actin levels in undifferentiated HL60 cells, depolymerization of the actin cytoskeleton with cytochalasin B did not affect increased expression of the 15/7 epitope on granulocytic HL60 cells. Cytochalasin B did, however, inhibit granulocytic HL60 adherence to fibronectin by 50%, demonstrating that actin polymeri zation is important for optimal β 1-dependent granulo cytic adherence. J. Leukoc. Biol. 57: 592–599; 1995.
GM-CSF and IL-2 share common control mechanisms in response to costimulatory signals in T cells
Authors: Shannon M Frances , Himes S Roy , Coles Leeanne S 
Published: January 2018

Abstract
Antigen complexed with major histocompatibility complex class I or II molecules on the surface of antigen presenting cells interacts with the T cell receptor (TCR) on the surface of T cells and initiates an activation cascade. So called costimulatory signals, mediated by other cell surface interactions or soluble cytokines produced by antigen presenting cells, are also required for complete T cell activation. High levels of cytokine gene expression in T cells also required both TCR and costimulatory signals. The granulocyte-macrophage colony-stimulating factor requires sequences in the promoter as well as a powerful enhancer located 3kb upstream to respond to TCR-like signals. These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells (NFAT). The activation of NFAT by TCR signals has been well described for interleukin-2 (IL-2) and IL4 gene transcription in T cells. Costimulatory signals, such as activation of the CD28 cell surface molecule on T cells, lead to activation through a distinct region of the granulocyte-macrophage colony-stimulating factor (GM-CSF) promoter. This region is termed the CK-1 or CD28RE and appears to bind specific members of the NF-κB family of transcription factors. Human T leukemia virus type 1 (HTLV-1) infects T cells and can lead to increase GM-CSF expression. We have found that the HTLV-1 transactivator protein, tax, acts as a costimulatory signal for GM-CSF and IL-2 gene transcription, in that it can cooperate with TCR signals to mediate high level gene expression. Tax activates the GM-CSF promoter through the CK-1/CD28RE region and also activates nuclear factor-κB binding to this region. However, other transcription factors or coactivators of NF-κB are required for tax activation but these remain to be identified. The CK-1/CD28RE of GM-CSF shows a high degree of similarity to the IL-2 CD28RE and the IL-3 gene also contains a related region. This observation, together with the fact that both GM-CSF and IL-2 respond to TCR signals via NFAT, implies a high degree of conservation in the regulation of cytokine gene expression in T cells. J. Leukoc. Biol. 57: 767-773; 1995.
Characterization of a non-granule associated pore-forming protein in agranular lymphocytes
Authors: Ortaldo J R , Wiltrout T A , Sayers T J , Yagita H , Winkler-Pickett R T 
Published: January 2018

Abstract
Recently, two populations of small lymphocytes (SL) have exhibited non-major histocompatibility complex (MHC) restricted lysis. Recent studies by numerous laboratories have demonstrated that resting T cells triggered through CD3 and CD28 costimulations can result in immediate, non-MHC restricted killing. Our recent studies with CD3-, CD56+ SL demonstrated that although these cells contained no cytoplasmic granules detected with electron microscopy, they mediated potent NK and ADCC activity. In the present study, we have used a Western blotting technique that allows for the detection and quantitation of total cellular levels of pore-forming protein (PFP). We have found that freshly isolated peripheral non-granulated lymphocytes (both CD3+ and CD3-) contain PFP. In addition, CD3- CD56+ SL contain levels of PFP similar to those of the highly granular CD3- LGL. In search of non-granule PFP, we exploited the rat NK (RNK) cell lines as a source of other potential cytotoxic factors. A membrane associated PFP, based on Western blotting, was isolated from rat RNK cells. Unlike PFP isolated from granules, this PFP was active after culture in Ca2+-containing medium. However, the lytic activity isolated from the non-granule PFP of RNK cells was inhibited by monoclonal antibodies to PFP. Collectively, these studies indicate that PFP is present in small agranular lymphocytes (both NK and T cells) and that it is not stored in large cytoplasmic granules. The implication of our results for the acquisition and activation of lytic ability in NK and T cells will be discussed. J. Leukoc. Biol. 57: 897–903; 1995.
Monocytes cultured in cytokine-defined environments differ from freshly isolated monocytes in their responses to IL-4 and IL-10
Authors: Hart Prue H , Jones Catherine A , Finlay-Jones John J 
Published: January 2018

Abstract
To investigate the regulatory effects of the prototypic Th2 lymphocyte products and potential immunotherapeutic agents interleukin-4 (IL-4) and IL-10 on macrophages differentiated in vitro under different cytokine-defined environments, blood monocytes were incubated for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor or IL-4. The effect of monocyte culture in the presence or absence of serum was also investigated. Functional responses by 7-day-cultured cells to IL-4, quantified as decreased CD 14 expression and suppression of lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) and IL-1β production, and as a positive response, increased CD23 expression, were compared directly with the responses by monocytes from which they were derived. In response to IL-10, decreases in LPS-induced TNF-α and IL-lβ production and reduction in the expression of major histocompatibility complex (MHC) class II antigens were examined. Seven-day cultured monocytes/macrophages showed (1) diminished TNF-α production in response to IL-10 but not EL-4 (2), diminished IL-1β production in response to both IL-4 and IL-10, and compared with fresh monocytes (3), diminished CD14 expression in response to IL-4, and (4) a lesser increase in CD23 expression in response to IL-4. This was the case regardless of the cytokine in the presence of which the cells had been cultured for 7 days. Monocytes cultured for 7 days in GM-CSF expressed increased levels of MHC class II and LPS-induced TNF-α and responded inefficiently to IL-10 for decreased MHC class II. The responses by monocytes cultured for 7 days with GM-CSF resemble the published properties of synovial fluid macrophages from patients with chronic inflammatory arthritis. The study highlights the complexity of monocyte/macrophage responses to the immunoregulatory cytokines IL-4 and IL-10 and concludes that responses to IL-4 and IL-10 by blood monocytes may not be representative of responses by their differentiated or activated counterparts. J. Leukoc. Biol. 57: 909–918; 1995.
The potential role of the macrophage colony-stimulating factor, CSF-1, in inflammatory responses: characterization of macrophage cytokine gene expression
Authors: Evans Robert , Kamdar Sonya J , Fuller Jane A , Krupke Debra M 
Published: January 2018

Abstract
In this report we report that recombinant human monocyte-macrophage colony-stimulating factor-1 (CSF-1) induces resident murine peritoneal cells (PCs) to transcribe several inflammatory cytokine genes, including interleukin (IL)-1α, IL-1β, IL-6, and granulocyte-macrophage CSF in a dose-dependent and time-related manner. Peak mRNA levels were seen between 4 and 6 h. CSF-1 did not modulate the expression of tumor necrosis factor-α mRNA. The serum content of the culture medium appeared to regulate both the extent of CSF-1-induced gene transcription and the adherence properties of the cells. Decreasing the serum concentration significantly reduced CSF-1-induced transcription and was associated with the rapid spreading of the majority of the adherent cells. This reduced sensitivity to CSF-1 was paralleled by a markedly lower levels of c-fms mRNA encoding the CSF-1 receptor. Induced gene transcription was followed by the release of large quantities of IL-6 only. IL-1 activity remained associated with the cells. Neither supernatant nor cell lysate granulocyte-macrophage CSF activity was inducible above the low levels associated with control cultures. Evidence that the mononuclear phagocytes, as opposed to B or T cells, were the targets of CSF-1 was obtained in two ways: (1) PCs from B6 scid/scid and NOD scid/scid mice consisting of 78–86% MAC-1+, F4/80+ cells and few B or T cells, as shown by flow cytometry analysis, released 5- to 10-fold more IL-4 in response to CSF-1 stimulation than B6 PCs, which contained 30% double-positive cells, and (2) pretreatment of B6 PCs with antibodies to the CSF-1 receptor blocked the CSF-1-induced secretion of IL-6. These data suggest that CSF-1 primes noninflammatory mononuclear phagocytes for a role in inflammatory responses but does not provide the necessary signals for either secretion or translation of all cytokines equally. J. Leukoc. Biol. 58: 99–107; 1995.
The role of chemokines in inflammatory joint disease
Authors: Kunkel Steven L , Lukacs Nickolas , Kasama Tsuyoshi , Strieter Robert M 
Published: January 2018

Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by the elicitation and activation of a number of leukocyte populations within both the synovial space and joint tissue. The recruited leukocytes subsequently play an instrumental role in synovial cell proliferation, pannus formation, and bone erosion. Although it is known that leukocytes are important participants in the evolving joint pathology, the mechanism responsible for the successful elicitation of cells to the joint is not clear. A number of studies have identified an association of specific cytokines, including chemokines, with active arthritis, but longitudinal analyses of cytokine expression and the causal role of these mediators have not been defined. Animal models and cell culture systems have proved useful in identifying the expression of various cytokines during the maintenance of chronic joint inflammation. In addition, animal models have provided important information regarding the kinetic production and contribution of specific mediators to the development of experimental arthritis. These studies provide insight into the potential mechanisms for leukocyte involvement in inflammatory joint disease.
Endogenously produced urokinase amplifies tumor necrosis factor-α secretion by THP-1 mononuclear phagocytes
Authors: Sitrin Robert G , Shoilenberger Susan B , Strieter Robert M , Gyetko Margaret R 
Published: January 2018

Abstract
This study examined the effects of endogenous urokinase (uPA) on lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) secretion in THP-1 mononuclear phagocytes. Anti-uPA monoclonal antibody (mAb) suppressed LPS-driven TNF-α secretion by 61.6 ± 5.9% (P &lt; .001), and PAI-1, a uPA inhibitor, suppressed it to 53.1 ± 8.2% of the control value (P &lt; .001). Up-regulation of TNF-α mRNA was suppressed in parallel with secreted TNF-α protein. TNF-α secretion was unaffected by depleting plasminogen or by aprotinin, a plasmin inhibitor. When endogenous uPA was displaced from the cell, exogenous high-molecular-weight (intact) uPA augmented LPS-driven TNF-α secretion. By contrast, a uPA fragment containing the catalytic domain was inhibitory, and the uPA receptor-binding domain had no effect. We conclude that endogenous uPA amplifies TNF-α neosynthesis of UPS-stimulated THP-1 mononuclear phagocytes. The effect requires intact uPA and is independent of plasmin activity. This represents a novel mechanism by which a mononuclear phagocyte–derived protease contributes to generating proinflammatory signals.
A monoclonal antibody to human macrophage gangliosides inhibits macrophage migration
Authors: Berenson Charles S , Patterson Melissa A , Pattoli Mark A , Murphy Timothy F 
Published: January 2018

Abstract
Gangliosides have diverse immunoregulatory properties. The gangliosides endogenous to macrophages may have immunoregulatory properties that distinguish them from other gangliosides. Gangliosides have been indirectly implicated in macrophage migration as putative cell surface receptors for migration inhibitory factor (MIF). In this study, a monoclonal antibody to human macrophage gangliosides (antibody 25F4) was developed and characterized. This is the first report of the development of monoclonal antibodies to gangliosides of macrophages of any species. Thin-layer chromatographic immunostaining indicated that antibody 25F4 recognized major gangliosides of human macrophages but did not recognize those previously identified as containing fucose. Immunofluorescent surface labeling of viable human macrophages indicated that antibody 25F4 recognized a surface-accessible epitope, present on all cells, and that this was abolished with lipid depletion of macrophage membranes. This epitope was not present on several human nonmacrophage cells. Finally, human macrophages pretreated with antibody 25F4 demonstrated striking inhibition of migration in an agarose droplet assay, whereas an irrelevant monoclonal antibody or monoclonal antibodies to nonganglioside surface epitopes of human macrophages had no effect on migration. Migration inhibition occurred even though antibody 25F4 was removed from the extracellular milieu and was not due to formation of cellular aggregates. These studies support a role for human macrophage gangliosides in macrophage migration.
In vitro culture of murine peritoneal and alveolar macrophages modulates phagocytosis of Pseudomonas aeruginosa and glucose transport
Authors: Everett Karin D E , Barghouthi Sameer , Speert David P 
Published: January 2018

Abstract
Phagocytosis by murine peritoneal macrophages (PMφ) of unopsonized Pseudomonas aeruginosa is a novel, glucose-dependent process occurring in concert with glucose or mannose transport via the GLUT1 facilitative transporter. The mechanism by which this transport triggers phagocytosis is not understood. The purpose of these investigations was to improve our understanding of this mechanism by delivery of an alternative sugar (fructose) to PMφ and to murine alveolar macrophages (AMφ). Fructose-cultured PMφ developed fructose-dependent phagocytosis of P. aeruginosa with increased glucose-dependent phagocytosis, GLUT1 expression, and [14C]glucose transport. Freshly explanted AMφ, which were unable to transport [41C]ghicose or to ingest P. aeruginosa acquired the ability to transport glucose and to phagocytose P. aeruginosa with culture in either glucose or fructose. Both fructose- and glucose-cultured AMφ remained viable but incapable of measurable fructose transport or fructose-dependent phagocytosis. These studies suggest that an intracellular metabolite of fructose, glucose, and mannose is involved in triggering macrophage phagocytosis of P. aeruginosa. We demonstrate that delivery of appropriate substrates can substantially improve AMφ phagocytic function and may therefore possibly improve pulmonary host defense against P. aeruginosa.
Differential regulation of Ia expression and antigen presentation by listeriolysin-producing versus non-producing strains of Listeria monocytogenes
Authors: Vazquez M A , Sicher S C , Proctor M L , Crowley J C , Lu C Y 
Published: January 2018

Abstract
listeria monocytogenes is an intracellular bacterial pathogen. A single gene product, listeriolysin (LLO), is critical for the induction of protective immunity. We now show that listeria that produce functional LLO augment Ia expression by macrophages and are better presented to a Th1, CD4+ anti-listeria T cell line. We used two genetically engineered strains of listeria which differed only in their ability (Ly+) or inability (Ly-) to produce functional LLO. Ia-negative murine macrophages ingested either Ly+ or Ly-, and then were stimulated by interferon-γ(IFN-γ). Increasing numbers of live Ly+, but not Ly-, augmented IFN-γ-induced Ia expression. Ly+ by itself did not induce Ia expression. Heat-killed Ly+ and Ly- did not augment IFN-γ-induced Ia expression. The abundance of Ia on the macrophage cell surface is one major determinant of antigen presentation to CD4+ T cells. Consistent with their ability to augment Ia expression, Ly+ were better presented than Ly- to a CD4+, Th1, anti-listeria T cell line. When macrophages and T cells were from different inbred mouse strains, antigen presentation required identity at the Class II region of the MHC gene complex. This indicated that antigen presentation occurred via Ia molecules. The increased ability of macrophages to present Ly+ is a product of the macrophage-listeria interaction, not a property of the T cell line 86. If Ia-negative macrophages ingested listeria and were then stimulated by IFN-γ, Ly+ was presented more efficiently than Ly-. On the other hand, if Ia-positive macrophages ingested Listeria, then Ly+ and Ly- were presented equally well to T cells. Altogether our data is consistent with the hypothesis that macrophages interact differently with Ly+, and that this contributes to the ability of only live Ly+-to induce protective immunity.
Development and characterization of a novel monoclonal antibody (mNI-11) that induces cell adhesion of the LPS-stimulated human monocyte-like cell line U937
Authors: Ikewaki Nobunao , Inoko Hidetoshi 
Published: January 2018

Abstract
A monoclonal immunoglobulin G1 (IgG1) antibody (mAb), designated mNI-11, was produced by immunizing mice with the lipopolysaccharide (LPS)-stimulated monocyte-like cell line U937. The reactivity of mNI-11 was tested by the indirect immunofluorescence method. The antigen defined by mNI-11 was found to be expressed on U937 cells, LPS-stimulated U937 cells, normal CD14+ cells (monocytes/macrophages), and human umbilical vein endothelial cells (HUVECs). Expression of the antigen defined by mNI-11 on HUVECs slightly increased in response to exposure to tumor necrosis factor-α (TNF-α) and phorbol myristate acetate (PMA). When the reactivity of mNI-11 and mAbs binding human differentiation antigens such as CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD49d, CD50, CD54, CD58, CD80, CD102, CD106, HLA-class I, or HLA-class II antigen was compared, no mNI-11 reactivity resembling that of these mAbs was found. mNI-11 markedly induced homotypic cell aggregation of U937 cells when they were stimulated with LPS. The mNI-11-induced aggregation of LPS-stimulated U937 cells, referred to as LPS-U937 cells, required neither Fc receptor engagement nor cross-linking of the antigen defined by mNI-11 because aggregation was induced by both F(ab’)2 fragments and monovalent F(ab/) fragments of mNI-11. The mNI-11-induced aggregation was blocked by the addition of ethylenediaminetetraacetate, and also when incubated at 4°. mAbs to CD11a/CD18 (lymphocyte-function associated antigen-1; LFA-1) and CD54 (intercellular adhesion molecule-1; ICAM-1) completely blocked the LPS-U937 cell aggregation induced by mNI-11. The IPS-U937 cell aggregation induced by mNI-11 was partially but not completely blocked by the protein kinase C inhibitors sphingosine and H-7, and was completely blocked by the protein-tyrosine kinase inhibitor genistein. Interestingly, mNI-11 markedly promoted LPS-U937 cell adhesion to HUVECs. The mNI-11-induced LPS-U937 cell adhesion to HUVECs was not reduced in the presence of LFA-1 (CD11a/CD18) or ICAM-1 (CD54) mAbs. On the other hand, IPS-U937 cells, whether treated with mNI-11 or not, sufficiently adhered to the extracellular matrix protein fibronectin, but not to laminin or collagen type I. However, mNI-11 did not markedly promote IPS-U937 cell adhesion to fibronectin. Adhesion of IPS-U937 cells treated with mNI-11 to fibronectin was completely blocked by CD29 (β chain of very late antigens) mAb. The surface antigen recognized by mNI-11 had a molecular size of ~97 kDa under non-reducing conditions and ~117 kDa under reducing conditions, as determined by immunoblotting analysis. We found that mNI-11 recognizes an adhesion-associated molecule distinct from any previously reported in terms of its pattern of cellular distribution and molecular weight, and also found that mNI-11 has activity which induces cell adhesion/aggregation of U937 cells when stimulated with LPS.
Novel actions of aspirin and sodium salicylate: discordant effects on nitric oxide synthesis and induction of nitric oxide synthase mRNA in a murine macrophage cell line
Authors: Kepka-Lenhart Diane , Chen Li-Chun , Morris Sidney M 
Published: January 2018

Abstract
Aspirin and sodium salicylate each inhibit to a similar extent the production of nitric oxide (NO) in the RAW 264.7 murine macrophage cell line following stimulation by either lipopolysaccharide (LPS) or interferon-γ(IFN-γ). The similar potencies of aspirin and sodium salicylate indicate that acetylation of cellular macromolecules is not essential for the observed effects. The failure of added prostaglandin E2 to overcome the effects of aspirin or sodium salicylate indicates that these effects are not simply the result of inhibition of prostaglandin synthesis. The inhibition of NO production occurs irrespective of the effect of these agents on induction of nitric oxide synthase (iNOS) mRNA by LPS or IFN-γ. Aspirin and sodium salicylate inhibit iNOS mRNA induction in LPS-stimulated cells but enhance iNOS mRNA induction in IFN-γ-stimulated cells. In contrast, these agents consistently inhibit induction of argininosuccinate synthetase mRNA in both LPS- and IFN-γ-stimulated cells. Concentrations of aspirin in the 3–10 mM range inhibit induced NO production and expression of iNOS protein without inhibiting induction of iNOS mRNA. Discordances between effects on NO synthesis and induction of iNOS mRNA indicate that aspirin and sodium salicylate have multiple sites of action in their effects on pathways that are involved in the production of NO by stimulated RAW 264.7 cells.