bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease
Authors: Czaja Mark J , Geerts Albert , Xu Jun , Schmiedeberg Phyllis , Ju Yue 
Published: January 2018

Abstract
Considerable evidence suggests that monocytes/macrophages play a crucial role in the process of liver injury and repair. Recent investigations have focused on the function of various macrophage-produced cytokines in liver disease. Much is still unknown, however, about the mechanism of macrophage recruitment and activation during liver disease. To further define this process, the gene expression of the monocyte chemoattractant monocyte chemoattractant protein 1 (MCP-1) was examined in animal and human liver disease. MCP-1 mRNA was not found in normal rat liver by Northern blot analysis. After single-dose treatments with the hepatotoxins carbon tetrachloride and galactosamine, MCP-1 mRNA was detectable beginning at 2 and 4 h after treatment, respectively, and was expressed continuously until 60–72 h. During chronic carbon tetrachloride administration, MCP-1 mRNA levels were elevated for the entire 10 weeks of treatment with peak levels of expression occurring early (weeks 1–3) and late (weeks 8–10) in this model. Isolated liver cell fractions from rats treated for 3 weeks with carbon tetrachloride revealed the major cellular source of MCP-1 mRNA to be fat-storing or Ito cells, with some expression occurring in the endothelial cell fraction. Studies of potential inducers of hepatic MCP-1 expression showed that lipopolysaccharide, tumor necrosis factor-α, and interleukin-lα and β treatments all led to MCP-1 expression. Finally, studies of human liver samples revealed MCP-1 gene expression in nondiseased liver and greatly increased levels in livers from patients with fulminant hepatic failure. These data implicate MCP-1 from fat-storing cells as a modulator of the process of liver injury and further support a role for MCP-1 in the pathogenesis of human disease. J. Leukoc. Biol. 55: 120–126; 1994.
Endocytosis of sulfatides by macrophages: relationship to the cellular uptake of phosphatidylserine
Authors: Greenspan Phillip , Gutman Robert L 
Published: January 2018

Abstract
These studies initially examined the effect of sulfatides on the endocytosis of phosphatidylserine (PS) liposomes in J774 macrophages employing liposomes composed entirely of PS and the nonexchangeable radiolabel [3H]cholesteryl hexadecyl ether. Bovine brain sulfatides significantly inhibited the uptake of PS liposomes by macrophages to a level of approximately 15% of control values. To examine whether macrophages were also capable of recognizing and internalizing sulfatides, sulfatide-containing liposomes were prepared using phosphatidylcholine (PC), cholesterol, and sulfatides (6:2:4 molar ratio) incorporating the same radiolabel. The sulfatide-containing liposomes were found to be avidly endocytosed by macrophages. Uptake of the sulfatide-containing liposomes by macrophages was significantly greater than the uptake of liposomes made without sulfatides. When the macrophages were incubated with the anionic compounds dextran sulfate and fucoidin, both the binding of the liposomes to the macrophages at 4° and the internalization of the liposomes at 37° were inhibited to approximately 10% of control values. The negatively charged phospholipids phosphatidylglycerol and cardiolipin significantly inhibited the uptake of sulfatide-containing liposomes, and PS was not effective in reducing the cellular uptake of these liposomes. Both oxidized low-density lipoprotein (LDL) and acetylated LDL reduced the uptake of the sulfatide-containing liposomes; the uptake observed in the presence of acetylated LDL and oxidized LDL was approximately 70% and 40%, respectively, of control values. These findings demonstrate that macrophages can efficiently endocytose both sulfatides and negatively charged phospholipids to remove them from the circulation. J. Leukoc. Biol. 55: 99–104; 1994.
Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells
Authors: Carter Wayne O , Naryanan Padma Kumar , Robinson J Paul 
Published: January 2018

Abstract
One of the objectives of studying endothelial cells in vitro is to evaluate neutrophil-endothelial cell interactions including potential consequences of oxidant-mediated damage to the endothelial cell. Current under-standing of endothelial cell oxidative function is derived primarily from the measurement of extracellular products. We utilized 2 dyes, 2′,7′-dichlorofluorescin diacetate (DGFH-DA) and hydroethidine (HE), which measure hydrogen peroxide (H2O2) and superoxide anion (O2-) respectively, for their suitability to monitor oxidative mechanisms in endothelial cells and to provide a reliable measure of intracellular oxidants. Endothelial cells stained with DCFH-DA and stimulated with H2O2 exhibited an increase in the fluorescent product 2′,7′-dichlorofluorescein (DCF) (measure of intracellular H2O2) which peaked at 10 min. Endothelial cells stained with HE and stimulated with H2O2 exhibited an increase in the fluorescent product ethidium bromide (EB) (measure of intracellular O2-) which lasted for approximately 60 min. Superoxide dismutase increased DCF fluorescence in endothelial cells stimulated with H2O2 by 158%. Allopurinol (xanthine oxidase inhibitor) reduced DCF and EB fluorescence by 48% and 37% respectively in endothelial cells stimulated with H2O2. Catalase completely inhibited an increase in DCF or EB fluorescence in endothelial cells stimulated with H2O2. There was a direct correlation between mean DCF and EB fluorescence intensity and the concentration of H2O2 or the number of phorbol 12-myristate 13-acetate-activated neutrophils added to endothelial cells. We conclude from these studies that DCFH-DA and HE can be used to measure intracellular H2O2 and O2- in endothelial cells and that the xanthine oxidase pathway for intracellular O2- production accounts for approximately 40% of the total intracellular O2- generated in endothelial cells after stimulation with H2O2. The combination of image cytometry and flow cytometry will be important for future evaluations of endothelial cell function. J. Leukoc. Biol. 55: 253–258; 1994.
Identification and characterization of human neutrophil carbonic anhydrase
Authors: Campbell Andrew R , Andress Dennis L , Swenson Erik R 
Published: January 2018

Abstract
Many functions of polymorphonuclear leukocytes (PMNs) appear to alter and be affected by changes in the intracellular and/or extracellular acid-base milieu, suggesting that carbonic anhydrase (CA) may be important. Although small amounts of CA activity in PMNs have been reported, it has not been characterized fully. We therefore studied isolated mature circulating human PMNs and cultured HL-60 cells, an undifferentiated myelopoietic cell line, and compared these to human red cells (RBCs) for CA activity. Activity and sulfonamide inhibition were measured by a modified micromethod assay. Isoenzyme and total CA concentrations were determined by radioimmunoassay for human isozyme CA I, differential inhibition by MK-927, inhibition by 0.2% sodium dodecyl sulfate (SDS), and quantitative sulfonamide binding. Total CA activity (units/106 cells) was 0.04 in PMNs, 0.06 in HL-60 cells, and 0.62 in RBCs. Human PMNs have a total CA concentration of 1.3 μM, of which 0.9 μM is CA I and the remainder is CA II. Total loss of CA activity with 100 μM ethoxzolamide and 0.2% SDS ruled out significant CA III or CA IV activity. Subcellular fractionation of PMNs revealed that all CA activity was cytosolic. The absence of CA activity in mitochondrial and microsomal membrane fractions argues against any mitochondrial CA V or membrane-bound CA IV contribution to total CA activity. Neutrophils contain both CA I and II isozymes in roughly the same proportion as RBCs but at much lower concentrations, suggesting that in the course of maturation the CA content of neutrophils is regulated differently from that in erythrocytes. J. Leukoc. Biol. 55: 343–348; 1994.
The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion
Authors: Granger D Neil , Kubes Paul 
Published: January 2018

Abstract
The accumulation of leukocytes in inflamed tissue results from adhesive interactions between leukocytes and endothelial cells within the microcirculation. These adhesive interactions and the excessive filtration of fluid and protein that accompanies an inflammatory response are largely confined to one region of the microvasculature: postcapillary venules. The nature and magnitude of the leukocyte–endothelial cell adhesive interactions that take place within postcapillary venules are determined by a variety of factors, including expression of adhesion molecules on leukocytes and/or endothelial cells, products of leukocyte (superoxide) and endothelial cell (nitric oxide) activation, and the physical forces generated by the movement of blood along the vessel wall. The contribution of different adhesion molecules to leukocyte rolling, adherence, and emigration in venules is discussed. Emerging views on potential endogenous antiadhesion molecules produced by endothelial cells as well as the influence of alterations in shear rate on leukocyte adhesion are addressed. Finally, the pathophysiological significance of the microvascular responses to inflammation are discussed in terms of adhesion-directed strategies for the treatment of different cardiovascular diseases and circulatory disorders. J. Leukoc. Biol. 55: 662–675; 1994.
The magnitude of HIV replication in monocytes and macrophages is influenced by environmental conditions, viral strain, and host cells
Authors: Chang Joon , Li Shan , Naif Hassan , Cunningham Anthony L 
Published: January 2018

Abstract
It has been difficult to standardize the effects of various stimuli on HIV replication in monocytes and macrophages in different laboratories. In this study we have shown that it is possible to standardize HIV inocula, culture conditions, and HIV antigen assay to achieve reproducibility with the same viral isolate and donor monocyte and macrophage. However, changes in serum concentration, in the strain of blood-derived isolate (even at low passage), in the donor source of the monocyte/macrophage, and in the state of cellular maturation all influenced HIV production by these cells. The donor source of monocytes contributed as much to variability in HIV production as the HIV strain and results were reproducible when the same source was used repeatedly. These in vitro data suggest that genetic differences may contribute to differences in HIV replication in macrophages and consequently to tissue virus load in vivo. J. Leukoc. Biol. 56: 230–235; 1994.
Molecular mechanisms of IL-4 effect on HIV expression in promonocytic cell lines and primary human monocytes
Authors: Naif Hassan , Ho-Shon Michael , Chang Joon , Cunningham Anthony L 
Published: January 2018

Abstract
HIV-1 can productively infect mononuclear phagocytes derived from blood, bone marrow, brain, and lung. Interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) have previously been shown to stimulate HIV replication in monocytes and macrophages. The mechanism of IL-4 stimulation was investigated and compared with the known effects of TNF-α. IL-4 up-regulated the expression of HIV mRNA within the first 2 days after infection of promonocytic U-937 cells and 3 to 4 days after infection of plastic-adherent blood macrophages with HIV-1. TNF-α also up-regulated production of HIV RNA but to a greater degree than IL-4, reaching a peak 3–4 days after addition. Northern blot analyses showed an increase in genomic and spliced RNAs at these times. However, there was reduced stimulation of HIV mRNA production when IL-4 and TNF-α were combined. These techniques are being used to further elucidate the mechanism of action of cytokines that inhibit HIV replication in purified human monocytes and macrophages. J. Leukoc. Biol. 56: 335–339; 1994.
L-Selectin mediates downregulation of neutrophil TNF receptors
Authors: Richter Johan , Zetterberg Eva 
Published: January 2018

Abstract
Tumor necrosis factor (TNF) is a potent activator of neutrophil granulocytes, which acts via two cell-surface receptors: the p55-TNF receptor (TNF-R55) and the p75-TNF receptor (TNF-R75). Proteolytic cleavage of the extracellular region of the receptors results in formation of soluble TNF-binding proteins, TNF-R55-BP and TNF-R75-BP. We recently reported that adherence alone, without any further stimuli, causes release of both TNF-R55-BP and TNF-R75-BP and that both leukocyte-integrin-dependent and non-integrin-dependent adherence mechanisms can modulate TNF receptor expression. In the present work we show that crosslinking of a mAb to the adhesion protein l-selectin (TQ1) on the surface of neutrophils results in downregulation of TNF-receptor binding capacity. Furthermore, when the fluctuations of cytosolic free calcium found in adherent neutrophils were blocked with the cell-permeable calcium chelator BAPTA, adherence-induced release of TNF-R55-BP was inhibited. We have shown that adherence, via mechanisms involving two adhesion proteins, l-selectin and the CD11/CD18 leukocyte integrins, and fluctuations of cytosolic free calcium, can result in downregulation of neutrophil TNF-receptors. J. Leukoc. Biol. 56: 525–527; 1994.
Apoptosis in leukocytes
Authors: Squier Margaret K T , Sehnert Amy J , Cohen J John 
Published: January 2018

Abstract
All cells of the hematopoietic system have finite life spans, shorter by far than that of the host. They end their lives by committing a form of cellular suicide or programmed cell death. The morphology of this process is considerably different from that of necrosis and is called apoptosis. Apoptotic cells undergo a stereotyped sequence of changes, including shrinkage and nuclear collapse. The cell is quickly recognized and eaten by a phagocyte, without the elicitation of an inflammatory response. Although most cells have specific triggers of apoptosis, the killer T cell seems able to induce apoptosis in any cell it recognizes. The process of apoptosis is regulated by cytokines, and may be modulated both in vitro and in vivo. J. Leukoc. Biol. 57: 2–10; 1995.
Cyclic GMP and guanylate cyclase mediate lipopolysaccharide-induced Kupffer cell tumor necrosis factor-α synthesis
Authors: Harbrecht Brian G , Wang Stewart C , Simmons Richard L , Billiar Timothy R 
Published: January 2018

Abstract
Tumor necrosis factor-α (TNF-α) is an important mediator in sepsis and septic shock. Kupffer cells (KCs) are the resident macrophages of the liver and are potent producers of TNF-α in response to inflammatory stimuli such as bacterial endotoxin or lipopolysaccharide (LPS). Although the effects of exogenous cytokines such as interferon-γ on TNF-α production by macrophages have been fairly well studied, the intracellular pathways regulating KC TNF-α synthesis are largely unknown. We investigated the role of guanylate cyclase and cGMP in LPS-induced KC TNF-α synthesis. Exogenous 8-BrcGMP and dbcGMP increased LPS-stimulated TNF-α synthesis but had no effect on KC TNF-α in the absence of LPS. Sodium nitroprusside (SNP), a nitric oxide-releasing substance that stimulates guanylate cyclase, increased TNF-α synthesis in response to LPS, whereas methylene blue and LY83583, guanylate cyclase inhibitors, decreased KC TNF-α synthesis. The inhibitory effect of methylene blue could be overcome with exogenous dbcGMP or SNP. Our results demonstrate that guanylate cyclase and cGMP mediate LPS-induced KC TNF-α synthesis and suggest that agents that alter cyclic nucleotide metabolism in KCs may affect the response of these cells to inflammation and inflammatory stimuli. J. Leukoc. Biol. 57: 297–302; 1995.
Regulation of L-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone
Authors: Burton Jeanne L , Kehrli Marcus E , Kapil Sushila , Horst Ronald L 
Published: January 2018

Abstract
The responsiveness of bovine neutrophil L-selectin and CD18 to in vivo glucocorticoid administration was characterized by flow cytometric analysis. Blood was sampled intensively from dairy cows treated for 3 days with placebo, cortisol, or dexamethasone. Immunostaining was performed on whole blood (100 μ1) that was left unstimulated or was stimulated with platelet-activating factor (PAF; 1 μg/ml blood) prior to incubation with fluorescein isothiocyanate-conjugated monoclonal antibodies against L-selectin and CD18. Results were expressed as the percentage of positive-staining cells and as mean fluorescence intensity (MFI) of those cells. Total leukocyte count and leukocyte differentials were also performed on all blood samples. Dexamethasone caused nearly complete down-regulation of L-selectin (P &lt; .01) on the surface of gated cells and reduced to half the MFI of CD18 (P &lt; .01). Compared with values for the placebo group, dexamethasone began to cause L-selectin down-regulation within 8 h after the first injection and these effects persisted until 48 h after the third injection. This was correlated in time with an acute reduction in the proportion of cells that stained positive for L-selectin (from 98% before dexamethasone injections to a low of 17% by 40 h after the first injection). Dexamethasone also caused leukocytosis and neutrophilia during this time interval. In contrast, CD18 down-regulation was delayed until 16 h after the second dexamethasone injection and persisted for roughly 8 days. However, at no time during the experiment did dexamethasone influence the proportion of gated cells staining positive for CD18 (always 100%). Effects of cortisol were generally similar in pattern to those of dexamethasone but were more subtle and more readily detected when PAF was added to blood prior to immunostaining. These results strongly suggest that one mechanism of the anti-inflammatory action of glucocorticoids is to induce dramatic down-regulation of L-selectin and CD18 adhesion molecules on blood neutrophils. J. Leukoc. Biol. 57: 317–325; 1995.
Soluble and membrane-anchored forms of the human IFN-α/β receptor
Authors: Novick Daniela , Cohen Batya , Tal Natan , Rubinstein Menachem 
Published: January 2018

Abstract
The recently cloned ligand binding component of the type I human interferon-α/β receptor (IFN-α/βR) and its soluble analogue (p40) were characterized. p40 is a potent inhibitor of type I IFNs and antibodies directed against p40 completely block the activity of type I IFNs in human cells. These antibodies immunoprecipitate cellular 102-kDa (major) and 51-kDa (minor) forms of IFN-α/βR. We find that the 51-kDa IFN-α/βR is a disulfide-linked subunit of the 102-kDa IFN-α/βR. Two types of cDNA clones were isolated and sequenced, a 1.5-kb cDNA coding for the transmembrane 51-kDa IFN-α/βR and a 4.5-kb cDNA coding for p40. In addition to ligand binding, IFN-α/βR is directly involved in signaling, because it becomes phosphorylated at Tyr residues on ligand binding and it is physically associated with the cytoplasmic tyrosine kinase JAK1. J. Leukoc. Biol. 57: 712–718; 1995.
Interruption of cytokine networks by poxviruses: lessons from myxoma virus
Authors: McFadden Grant , Graham Kathryn , Ellison Kimberly , Barry Michele , Macen Joanne , Schreiber Martha , Mossman Karen , Nash Piers , Lalani Alshad , Everett Helen 
Published: January 2018

Abstract
Myxoma virus is an infectious poxvirus pathogen that induces a virulent systemic disease called myxomatosis in European rabbits. The disease is rapidly and uniformly fatal to susceptible rabbits and is characterized by generalized dysfunction of cellular immunity and multiple interruptions of the host cytokine network. A number of virus genes are classified as virulence factors because virus constructs bearing targeted gene disruptions induce attenuated disease symptoms. Many of these genes encode proteins that interact directly with effector elements of the host immune system. Included among these immunosubversive viral proteins are secreted mimics of host ligands or regulators (virokines) and homologues of cellular cytokine receptors (viroceptors). Five examples of these immune modulator proteins encoded by myxoma virus are reviewed: (1) myxoma growth factor, a member of the epidermal growth factor ligand superfamily; (2) SERP-1, a secreted serine proteinase inhibitor; (3) M11L, a receptor-like surface protein; (4) T2, a tumor necrosis factor receptor homologue; and (5) T7, an interferon-γ receptor homologue. The origin of viral strategies designed to subvert immune regulation by host cytokines is considered in the context of the biology of myxoma virus within immunocompetent hosts. J. Leukoc. Biol. 57: 731–738; 1995.
IL-15, a novel T cell growth factor that shares activities and receptor components with IL-2
Authors: Giri Judith G , Anderson Dirk M , Kumaki Satoru , Park Linda S , Grabstein Kenneth H , Cosman David 
Published: January 2018

Abstract
Interleukin 15 is a newly discovered cytokine that shares biological activities with IL-2 and, like IL-2, is a member of the four-helix bundle cytokine family. We have shown that IL-15 shares components of the receptor for IL-2: the α chain of the IL-2R is not required, but both the β and γ chains are needed for EL-15 mediated bioactivities. A defect in IL-15 signaling may therefore contribute to the phenotype of X-linked severe combined immunodeficiency in humans, resulting from mutations in the common γ chain. Differential ability of cells to bind and respond to IL-2 and IL-15 suggested the existence of an additional IL-15 specific receptor component. We identified an IL-15 specific binding protein (IL-15Rα) on a murine T cell and isolated the corresponding cDNA. The IL-15Rα is not a member of the hematopoietin receptor superfamily, but is structurally related to the α chain of the IL-2R. Differences in the expression pattern of EL-15 and its receptor compared to the EL-2 system suggest unique in vivo roles for IL-15. J. Leukoc. Biol. 57: 763–766; 1995.
CAP37, a neutrophil-derived multifunctional inflammatory mediator
Authors: Pereira H Anne 
Published: January 2018

Abstract
Cationic antimicrobial protein of M r 37 kDa (CAP37) is a multifunctional protein isolated from the granules of human neutrophils, which has important implications in host defense and inflammation. CAP37 was initially recognized for its strong antibiotic activity against Gram-negative bacteria and was viewed as a component of the oxygen-independent killing mechanism of the neutrophil. However, we now know that CAP37 has more far reaching and important functions. It is a physiological protein released during inflammation with a high potential of regulating monocyte/macrophage functions, such as chemotaxis, increased survival, and differentiation. Recently, it has been demonstrated that CAP37 binds endotoxin. It has the structure of a serine esterase but lacks enzymatic activity. The bactericidal and endotoxin binding domains of the molecule have been delineated. The identification of functional peptides should provide new insight into the mechanisms of endotoxin binding, antimicrobial activity, and chemotaxis and in the long term provide key insights into therapies for treating infections and endotoxic shock. J. Leukoc. Biol. 57: 805–812; 1995.