bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of macrophages in the immunotherapy of Lewis lung peritoneal carcinomatosis
Authors: Wallace Paul K , Morahan Page S 
Published: January 2018

Abstract
The underlying cellular mechanisms for the antitumor effects of biological response modifiers (BRMs) have not been clearly resolved. We have investigated this issue in the Lewis lung (3LL) peritoneal carcinomatosis model in which treatment with the BRM MVE-2 slows tumor growth and enhances survival. MVE-2 is a potent inducer of cytotoxic macrophages (mφs); however, the in vivo tumoricidal properties of these mφs remain to be firmly established. To directly establish that mφs were at least in part responsible for the in vivo efficacy of MVE-2, a novel method of obtaining highly enriched mφ suspensions was developed which gave high purity, satisfactory yield, and excellent viability without affecting antitumor activity. Using the 3LL peritoneal carcinomatosis model and adoptive transfer techniques, we directly demonstrate that the majority of antitumor activity was associated with the adherent cell fraction enriched for mφs. Histological observations supported this conclusion, indicating that MVE-2 treatment initially activated cells associated with nonspecific immunity, retarding tumor growth in the ascites long enough for a multifaceted immune response to develop. J. Leukoc. Biol. 56: 41–51; 1994.
Changes in subcellular localization and surface expression of L-selectin, alkaline phosphatase, and Mac-1 in human neutrophils during stimulation with inflammatory mediators
Authors: Borregaard Niels , Kieldsen Lars , Sengelo Henrik , Diamond Michael S , Springer Timothy A , Anderson H Clarke , Kishimoto Takashi K , Bainton Dorothy F 
Published: January 2018

Abstract
The localization of the adhesion protein L-selectin in human neutrophils was determined by sub-cellular fractionation and immunoelectron microscopy and compared with the localization of Mac-1 (α m β z ) and alkaline phosphatase, the marker for secretory vesicles. L-selectin was found to be localized exclusively on the plasma membrane of unstimulated cells and also of stimulated cells, although markedly diminished. This was in contrast to Mac-1, which was also localized in secretory vesicles and in specific/gelatinase granules as shown previously [Sengeiov, H., et al. J. Clin. Invest. (1993) 92, 1467–1476]. Stimulation of neutrophils with inflammatory mediators such as tumor necrosis factor (TNF), platelet-activating factor (PAF), or f-Met-Leu-Phe (fMLP), induced parallel up-regulation of the surface membrane content of alkaline phosphatase and Mac-1 and down-regulation of L-selectin, as evidenced by flow cytometry. Preimbedding immunoelectron microscopy confirmed that L-selectin was present mainly on tips of microvilli in unstimulated cells and showed that alkaline phosphatase and Mac-1 were randomly distributed on the surface membrane of fMLP-stimulated cells. These studies indicate that the transition of neutrophils from L-selectin-presenting cells to Mac-l-presenting cells induced by inflammatory mediators is mediated by incorporation of secretory vesicle membrane, rich in Mac-1 and devoid of L-selectin, into the plasma membrane. J. Leukoc. Biol. 56: 80–87; 1994.
HIV replication in chronically infected macrophages is not inhibited by the Tat inhibitors Ro-5-3335 and Ro-24-7429
Authors: Dunne Amanda L , Siregar Hanni , Mills John , Crowe Suzanne M 
Published: January 2018

Abstract
Human immunodeficiency virus infects different cell types including CD4+ lymphocytes and monocyte-derived macrophages (MDMs). We have examined the activity of the HIV-1 Tat inhibitors Ro-5-3335 and Ro-24-7429 in cultured human peripheral MDMs. Monocytes were isolated from HIV-seronegative donors by gradient centrifugation and plastic adherence. MDMs and unfractionated peripheral blood mononuclear cells (PBMCs) were infected with HIV Ba-L and then treated with drug either immediately (acute infection) or after 4 days (PBMCs) or 14 days (MDMs) (chronic infection). Inhibition of HIV replication by each drug was assessed by quantitation of HIV p24 antigen in culture supernatant using an enzyme immunoassay. In acutely infected MDMs, Ro-5-3335 (10 μM) and Ro-24-7429 (10 μM) resulted in 77% and 99% mean inhibition, respectively, of HIV replication with a clear dose response at lower concentrations; chronically infected MDMs were much less susceptible to these drugs, with both compounds inhibiting p24 antigen production by less than 50% at 10 μM. The drugs had no deleterious effect on cell viability at any concentration tested. In acutely infected PBMCs Ro-5-3335 and Ro-24-7429 resulted in 68% and 68.5% mean inhibition at 10 μM; when the compounds were added 4 days after infection inhibition was less than 50% compared with controls. Thus, the Tat inhibitors were effective in inhibiting acute HIV infection in MDMs but not in chronically infected cells, findings that differ from those of published studies using continuous lymphoblastoid cell lines. J. Leukoc. Biol. 56: 369–373; 1994.
Unaggregated serum IgA binds to neutrophil FcαR at physiological concentrations and is endocytosed but cross-linking is necessary to elicit a respiratory burst
Authors: Stewart Wilson W , Mazengera Ronald L , Shen Li , Kerr Michael A 
Published: January 2018

Abstract
My43 is a monoclonal antibody directed against FcαRs on monocytes that also recognizes neutrophil (PMN) FcαRs and is able to elicit a respiratory burst in purified cells. It appears to be directed against the immunoglobulin A (IgA) binding site of FcαRs or an epitope in close proximity, since IgA and My43 compete for binding to PMNs. My43 immunoblotted FcαR that had been affinity purified from PMN membranes and immunoprecipitated a 50–70 kDa protein from radiolabeled PMN membranes, apparently identical to that purified on IgA-Sepharose. These results suggest the presence of a single class of FcαR on PMNs. Binding of unaggregated monomeric or dimeric serum IgA to FcαRs on PMNs occurs at physiological concentrations, suggesting that in vivo FcαRs are saturated with ligand. This binding does not elicit a respiratory burst. Purified PMNs do not express surface IgA, since receptor-bound IgA is lost from the cell surface by endocytosis at room temperature although not at 4°. Rapid endocytosis of receptor-bound IgA has been demonstrated by flow cytometry and confocal microscopy. Unoccupied receptor that is able to bind IgA or My43 is subsequently reexpressed. Cross-linking of surface-bound IgA using F(ab’)2 anti-α chain antibodies triggers an oxidative burst. After internalization of the surface IgA the same F(ab’)2 anti-α chain antibodies do not trigger the burst. J. Leukoc. Biol. 56: 481–487; 1994.
Jacalin, a lectin that inhibits in vitro HIV-1 infection, induces intracellular calcium increase via CD4 in cells lacking the CD3/TcR complex
Authors: Lafont Virginie , Dornand Jacques , d’Angeac Arnaud Dupuy , Monier Serge , Alcover Andrès , Favero Jean 
Published: January 2018

Abstract
The lectin jacalin interacts with the CD4 cell surface antigen; this lectin inhibits in vitro infection by human immunodeficiency virus type 1 without preventing virus binding on the host cell. The infection process is known to involve cellular events triggered by the binding of the viral external glycoprotein gp120 to CD4. Herein we demonstrate that jacalin induces cell signaling directly through the CD4 antigen and that independently of the CD3/TcR complex. The capacity of jacalin to trigger cell signals through the CD4 molecule is discussed in relation to its ability to inhibit HIV infection. J. Leukoc. Biol. 56: 521–524; 1994.
The role of diacylglycerol and ceramide in tumor necrosis factor and interleukin-1 signal transduction
Authors: Schütze Stefan , Machleidt Thomas , Krönke Martin 
Published: January 2018

Abstract
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are cytokines with pleiotropic biological activities, exerting a broad range of overlapping biological functions. The redundancy of TNF and IL-1 activities may be based on the utilization of shared key components of intracellular signaling pathways. Two lipid second messengers have been found to transmit TNF and IL-1 intracellular signals: 1,2-diacylglycerol (DAG), generated by a phosphatidylcholine-specific phospholipase C, and ceramide, generated by sphingomyelinase (SMase). DAG is a well established activator of the important signaling system protein kinase C (PKC), which appears to mediate various cellular responses to TNF or IL-1. In addition, it is obvious that DAG also activates other enzyme systems like acidic sphingomyelinase. SMases have been implicated in a number of TNF responses, including stimulation of cell growth and differentiation, as well as triggering cytotoxicity and apoptosis. The metabolic active cleavage product of SMase, ceramide, is a novel multifunctional lipid second messenger capable of inducing various signaling systems. Both cytokines, TNF and IL-1, stimulate a neutral, plasma membrane-associated SMase that leads to stimulation of a protein kinase and eventually to activation of the mitogen-activated protein (MAP) kinase cascade and phospholipase A2. Ceramide is also capable of stimulating a cytosolic protein phosphatase. PKC plays a role in activation of the nuclear transcription factor AP-1, and the DAG-regulated acidic SMase is involved in transducing TNF signals to the cell nucleus via activation of the nuclear transcription factor NF-xB. J. Leukoc. Biol. 56: 533–541; 1994.
Multiple functions of nitric oxide in pathophysiology and microbiology: analysis by a new nitric oxide scavenger
Authors: Maeda Hiroshi , Akaike Takaaki , Yoshida Masaki , Suga Moritaka 
Published: January 2018

Abstract
A wide range of biological functions of nitric oxide (NO) was analyzed using a newly discovered nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-l-oxyl-3-oxide (PTIO) or its water-soluble derivative carboxy-PTIO. The chemistry is very simple in that NO was oxidized by PTIO, yielding one mole each of NO2 and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl. Based on the potent NO-scavenging activity of PTIO derivatives, the diverse functions of NO under physiological states as well as various pathological conditions such as endotoxin shock and viral diseases are now explicated. It was found that PTIO and carboxy-PTIO showed significant inhibitory activity against a series of biological actions of NO: (1) endothelium-dependent vascular relaxation in an ex vivo system, (2) pathogenicity of NO produced excessively in endotoxin shock in rats and in influenza virus pneumonitis in mice, and (3) enhanced vascular permeability in solid tumors mediated by NO. PTIO directly extinguishes NO generated by NO synthase (NOS) without affecting NOS activity, which is a clear contrast to NOS inhibitors. Therefore, characterization of this unique mode of action of PTIO appears to be helpful not only in understanding of the pathophysiological role of NO but also in the treatment of various diseases caused by excessive production of NO. J. Leukoc. Biol. 56: 588–592; 1994.
Summary of the 5TH International Congress on TNF and related cytokines: scientific advances and their medical applications1
Authors: Beutler Bruce 
Published: January 2018

Abstract
Ten years ago, a new field emerged with the isolation and cloning of tumor necrosis factor (TNF), an exceptionally pleiotropic cytokine that seemed to promise an effective treatment for cancer. The field drew a heavy following from the existing disciplines of immunology, oncology, endocrinology, hematology, and infectious disease research as it was recognized that the actions of TNF were relevant to each. The first International Congress on TNF and Related Cytokines was held in Heidelberg in 1986, and subsequent congresses were held in Napa, Chiba, and Veldhoven. This, the 5th Congress, was held at the Asilomar Conference Center in Monterey.
Lymphocyte-mediated nitric oxide production by rat endothelial cells
Authors: Shuler Randy L , Laskin Debra L , Gardner Carol R , Feder Lisa S , Laskin Jeffrey D 
Published: January 2018

Abstract
Lymphocyte migration from the blood to sites of tissue injury is mediated, in part, through the interaction of these cells with endothelial cells lining the vessel walls. The ability of endothelial cells to produce nitric oxide may be important in this process. We found that the addition of the nonspecific lymphocyte activators lipopolysaccharide (LPS) or concanavalin A (Con A) to rat hepatic endothelial cell cultures from control or endotoxemic rats markedly enhanced the ability of these cells to produce nitric oxide. In contrast, wheat germ agglutinin (WGA) and phytohemagglutinin (PHA) had no effect on nitric oxide release. Coculture of endothelial cells with lymphocyte-rich preparations of rat thymocytes or splenocytes stimulated endothelial cell nitric oxide production. This response was enhanced by LPS or Con A and to a lesser extent by WGA or PHA. In contrast to endothelial cells, thymocytes and splenocytes did not produce nitric oxide either in the presence or absence of lymphocyte mitogens. Increased production of nitric oxide by endothelial cells in response to lymphocytes and lymphocyte mitogens was due, at least in part, to increased expression of protein for an inducible form of nitric oxide synthase, as measured by Western blotting. Stimulation of endothelial cell nitric oxide production by thymocytes and splenocytes was inheritable by the specific nitric oxide synthase inhibitor NG-monomethyl-L-arginine and dependent on cell-cell contact. Thus, nitric oxide production by endothelial cells was reduced when the lymphocytes were physically separated from the endothelial cells using cell culture inserts. We hypothesize that nitric oxide released by endothelial cells increases vascular permeability, thereby allowing the extravasation of lymphocytes into the surrounding tissue, a process that may be important in inflammation, tissue injury, and/or wound healing. J. Leukoc. Biol. 57: 116–121; 1995.
Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS
Authors: Sato Kiminori , Miyakawa Kazuhisa , Takeya Motohiro , Hattori Ryuichi , Yui Yoshiki , Sunamoto Mie , Ichimori Yuzo , Ushio Yukitaka , Takahashi Kiyoshi 
Published: January 2018

Abstract
An antirat monoclonal antibody (mAb) against inducible nitric oxide synthase (iNOS), ANOS11, was used for immunohistochemistry to examine the expression of iNOS in various organs and tissues of adult rats in experimental endotoxic shock induced by lipopolysaccharide (LPS) injection. The phenotype of iNOS-expressed cells was also examined immunohistochemically using various mAbs. In control rats, very few cells were positive for ANOS11 except in the thymus. After intravenous injection of LPS, the number of iNOS-positive cells increased rapidly in almost all organs, except the thymus and brain, peaked 6 h after the injection, and decreased slowly. Of the numerous inflammatory cells that infiltrated the lungs, liver, and spleen after LPS injection, many were positive for ANOS11. Besides inflammatory cells, hepatocytes and endothelial cells of the aorta were also positive for ANOS11 but only around 6 h after injection. The cellular composition of iNOS-positive infiltrated cells changed along with the progression of endotoxic shock. At 4 to 6 h after injection, most iNOS-positive cells were considered polymorphonuclear leukocytes judging by their positive reactivity to 0X42 and their nuclear morphology. The population of iNOS-positive macrophages positive for EDI or ED2 increased with time. After 24 h, many iNOS-positive macrophages were found around the focal necrosis in the liver and spleen. These results indicate that the expression of iNOS in neutrophils, endothelial cells, and hepatocytes precedes that of macrophages in experimental endotoxic shock. The expression of iNOS in various cells and organs is closely associated with the progress and pathological changes of endotoxic shock. J. Leukoc. Biol. 57: 36–44; 1995.
Heterodimers of the calcium-binding proteins MRP8 and MRP14 are expressed on the surface of human monocytes upon adherence to fibronectin and collagen. Relation to TNF-α, IL-6, and superoxide production
Authors: Mahnke Karsten , Bhardwaj Ranjit , Sorg Clemens 
Published: January 2018

Abstract
The 27E10 antigen is a heterodimer of MRP8 and MRP14, two Ca2+-binding proteins related to the S-100 protein family. Previous studies have shown that 27E10 epitope–bearing monocyte subsets are prevalent in early acute but absent in chronic inflammatory conditions. These observations further provide an impetus for identifying the cellular mechanisms responsible for the appearance of different monocyte subpopulations during inflammation. Therefore this in vitro study was carried out to investigate the influence of adhesion in inducing 27E10-positive subsets. In adhesion assays the role of 27E10 antigen in spontaneous adherence was obvious, as a monoclonal antibody directed against the 27E10 antigen significantly inhibited the adherence of monocytes to collagen and fibronectin. In contrast, these extracellular matrix (ECM) proteins induce the cell surface expression and association of 27E10 antigen with cytoskeleton (CSK), detected by flow cytometry and confocal laser scan microscopy, respectively. Similar results were obtained on cross-linking with specific antibodies, thus showing involvement of the integrin molecules VLA-2 and VLA-4. In addition, the association with CSK could be confirmed by differential detergent extraction. The observed redistribution of 27E10 antigen guided by collagen compared with fibronectin was also paralleled by an augmented release of inflammatory cytokines interleukin-6, tumor necrosis factor α, and superoxide anions. Thus, this study demonstrates that under inflammatory conditions the interactions of extravasating monocytes with the ECM may induce an activated phenotype of monocytes marked by 27E10. J. Leukoc. Biol. 57: 63–71; 1995.
The endoperoxides/TxA2 analogue, U46619, inhibits human polymorphonuclear leukocyte function
Authors: Rotondo Serenella , Celardo Antonio , Evangelista Virgilio , Cerletti Chiara 
Published: January 2018

Abstract
The effects of the stable analogue of TxA2, U46619, on polymorphonuclear leukocyte (PMN) function were investigated. U46619, at micromolar concentrations, inhibited fMLP-stimulated aggregation, β-glucuronidase release, and superoxide production. fMLP-induced LTB4 synthesis was also inhibited. U46619 did not modify intracellular Ca2+ increase induced by fMLP in Fura-2-loaded PMN, suggesting that early events of cell activation were not involved. In fact, U46619 also inhibited aggregation, β-glucuronidase release, superoxide anion and LTB4 production induced by the calcium ionophore A23187. By comparison with the specific 5-lipoxygenase inhibitor, L-663,536, which prevented LTB4 synthesis without affecting degranulation, we excluded the impairment of PMN function by U46619 as a consequence of the reduction of this endogenous agonist. TLC separation of lipid extracts from [3H]-AA-loaded PMN, stimulated by A23187, showed significant reduction of the radioactivity associated with authentic free AA, suggesting that U46619 could interfere with mechanisms regulating AA release from membrane phospholipids. This suggestion is also supported by the observation that manoalide, a standard inhibitor of phospholipase A2, similarly to U46619, inhibits β-glucuronidase release from stimulated PMN. Prostaglandin endoperoxides, produced by cells participating in inflammatory reactions, might therefore play a role in modulating PMN activities. J. Leukoc. Biol. 57: 72–79; 1995.
Delayed-type hypersensitivity to a recombinant mycobacterial antigen, MPB64, in guinea pigs sensitized to Mycobacterium tuberculosis or Mycobacterium bovis BCG
Authors: Haga Shinji , Yamaguchi Ryuji , Nagai Sadamu , Matsuo Kazuhiro , Yamazaki Akihiro , Nakamura Reiko M 
Published: January 2018

Abstract
Recombinant MPB64 (rMPB64), a mycobacterial antigen, was obtained from an Escherichia coli clone transformed with a recombinant expression vector, pMAL64c. The rMPB64 was examined for the activity to elicit delayed-type hypersensitivity (DTH) in guinea pigs injected with live Mycobacterium tuberculosis H37Rv or live M. bovis BCG Tokyo. It was found that rMPB64 has the same reactivity as native MPB64 (nMPB64) or MPT64 (nMPT64) and the potency to elicit DTH was 13.4 times higher than that of PPD. Because MPB64 is secreted only by living M. tuberculosis and some strains of BCG, it is possible to use this antigen for the diagnosis of tuberculosis. J. Leukoc. Biol. 57: 221–225; 1995.
Modulation of rat neutrophil functions by administration of granulocyte colony-stimulating factor
Authors: Murata Kotaro , Watanabe Tadashi , Yamashita Takao , Gon Songi , Sendo Fujiro 
Published: January 2018

Abstract
Neutrophil function was examined in rats treated with recombinant human granulocyte colony-stimulating factor (G-CSF) using peripheral blood neutrophils (PBNs) and peritoneal exudate neutrophils (PENs) as sources of cells examined in vitro. Adherence to plastic plates containing fetal calf serum of nonstimulated or N-formylmethionyl-leucyl-phenylalanine (fMLP)- or tumor necrosis factor-α-stimulated PBNs obtained from G-CSF-injected rats was lower than that of control rats. In contrast, this adherence was higher in G-CSF-treated rats than in the control group when PENs were used. Neutrophil adherence of G-CSF-injected and noninjected groups was identical when phorbol myristate acetate was used to stimulate neutrophils. Superoxide production of PBNs stimulated with fMLP in vitro was lower in G-CSF-treated rats than in control rats but higher than in the controls when PENs were used. Furthermore, in vitro tumor cell growth inhibition by PBNs was lower in G-CSF-treated rats than in control rats, but when PENs were used inhibition was higher than in the controls. J. Leukoc. Biol. 57: 250–256; 1995.
An inhibitor of polyamine biosynthesis impairs human polymorphonuclear leukocyte priming by tumor necrosis factor α
Authors: Walters John D , Cario Anthony C , Leblebicioglu Binnaz , Fernandez Marilyn C , Marucha Phillip T 
Published: January 2018

Abstract
TNF primes polymorphonuclear leukocytes (PMNs) for enhanced oxidative and secretory activity and directly induces adhesion and IL-1β expression. Previous reports suggest that polyamine biosynthesis by ornithine decarboxylase (ODC) has an essential role in macrophage activation by TNF. In the current study, TNF induced rapid increases in the putrescine and spermine content of PMNs. Difluoromethylornithine (DFMO), a selective inhibitor of ODG, inhibited these increases and blunted the enhancement of superoxide generation and secondary granule release associated with priming by TNF. DFMO did not affect the expression of TNF receptors or block receptor-independent activation of the respiratory burst by phorbol esters. Moreover, DFMO did not antagonize induction of adhesion or IL-1β mRNA expression by TNF. Thus, polyamine biosynthesis plays an important role in priming by TNF, but is not involved in all PMN responses to this cytokine. This suggests that ODC is a potential target for selective chemotherapeutic modulation of the inflammatory response. J. Leukoc. Biol. 57: 282–286; 1995.