bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants
Authors: Spiecker Martin , Darius Harald , Kaboth Katharina , Hübner Felix , Liao James K 
Published: January 2018

Abstract
Although nitric oxide (NO) and antioxidants inhibit adhesion molecule expression, their inhibitory effects on nuclear factor κB (NF-κB) activation may differ. The NO donors, but not 8-bromo-cGMP, decreased tumor necrosis factor α (TNF-α)-induced VCAM-1, ICAM-1, and E-selectin expression by 11-70%. In contrast, NAC completely abolished VCAM-1 and E-selectin expression and decreased ICAM-1 expression by 56%. Gel shift assays demonstrate that NF-κB activation was inhibited by both NO and antioxidants. The activation of NF-κB involves the phosphorylation and degradation of its cytoplasmic inhibitor IκB-α by 26S proteasomes. The 26S proteasome inhibitor MG132 prevented the degradation of phosphorylated IκB-α. NAC inhibited IκB kinase (IKK) activity and prevented IκB-α phosphorylation and degradation. In contrast, NO did not inhibit IKK activity, IκB-α phosphorylation, or IκB-α degradation. However, NO, but not antioxidants, induced IκB-α promoter activity. The inhibitory effects of NO on adhesion molecule expression, therefore, differs from that of antioxidants in terms of the mechanism by which NF-κB is inactivated.
Hypoxia down-regulates MCP-1 expression: implications for macrophage distribution in tumors
Authors: Negus Rupert P M , Turner Lynn , Burke Frances , Balkwill Frances R 
Published: January 2018

Abstract
Monocyte chemoattractant protein 1 (MCP-1) is likely to contribute to the macrophage infiltrate in human ovarian carcinomas. Although MCP-1 is predominantly expressed by the tumor parenchyma, macrophages accumulate at highest density in necrotic regions, which are associated with low oxygen tensions. Tumor necrosis factor α (TNF-α) can stimulate MCP-1 production and is also present within ovarian carcinomas. We have investigated the effect of hypoxia both on MCP-1 expression in ovarian cancer cell lines and monocyte migration. Hypoxia down-regulated TNF-α-induced MCP-1 mRNA and protein production by ovarian cancer cells. The effect was mimicked by cobalt chloride and desferrioxamine, consistent with a specific oxygen-sensing mechanism. Unlike antioxidants, hypoxia did not inhibit nuclear factor κB mobilization. Monocyte migration in response to MCP-1 was also diminished under hypoxic conditions. Down-regulation of MCP-1 expression and the inhibition of monocyte migration are independent effects of hypoxia that may contribute to the distribution of macrophages within ovarian tumors.
CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells
Authors: Lahdenpohja Nina , Hurme Mikko 
Published: January 2018

Abstract
We have analyzed the effect of complete T cell activation (anti-CD3 plus anti-CD28) on the activation of NF-κB in CD45RA+ (naive) and CD45RO+ (memory/effector) T cells. Long exposure (24 h) induced stronger NF-κB DNA binding in CD45RA+ cells than in CD45RO+ cells. Analysis of the nuclear c-Rel protein indicated that after anti-CD3+anti-CD28 stimulation the level of c-Rel was higher in CD45RA+ cells. Analysis of the cytoplasmic inhibitor IκBα indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation in CD45RA+ cells but in CD45RO+ cells the degradation process was more rapid. Because the CD28 costimulus is known to induce the production of reactive oxygen intermediates (ROIs), the intracellular ROI levels in CD45RA+ and CD45RO+ cells were compared by flow cytometry. ROIs were produced in both cell types, but more strongly in CD45RA+ cells. The data presented in this study further emphasize the differences between CD45RA+ and CD45RO+ T lymphocytes in ROI-dependent signaling pathways.
The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense
Authors: Elsbach Peter 
Published: January 2018

Abstract
The bactericidal/permeability-increasing protein (BPI) is a 456-residue cationic protein produced only by precursors of polymorphonuclear leukocytes (PMN) and is stored in the primary granules of these cells. The potent (nM) cytotoxicity of BPI is limited to gram-negative bacteria (GNB), reflecting the high affinity (&lt;10 nM) of BPI for bacterial lipopolysaccharides (LPS). The biological effects of isolated BPI are linked to complex formation with LPS. Binding of BPI to live bacteria via LPS causes immediate growth arrest. Actual killing coincides with later damage to the inner membrane. Complex formation of BPI with cell-asssociated or cell-free LPS inhibits all LPS-induced host cell responses. BPI-blocking antibodies abolish the potent activity of whole PMN lysates and inflammatory fluids against BPI-sensitive GNB. The antibacterial and the anti-endotoxin activities of BPI are fully expressed by the amino terminal half of the molecule. These properties of BPI have prompted preclinical and subsequent clinical testing of recombinant amino-terminal fragments of BPI. In animals, human BPI protein products protect against lethal injections of isolated LPS and inocula of GNB. Phase I trials in healthy human volunteers and multiple Phase I/II clinical trials have been completed or are in progress (severe pediatric meningococcemia, hemorrhagic trauma, partial hepatectomy, severe peritoneal infections, and cystic fibrosis) and two phase III trials (meningococcemia and hemorrhagic trauma) have been initiated. In none of &gt;900 normal and severely ill individuals have issues of safety or immunogenicity been encountered. Preliminary evidence points to overall benefit in BPI-treated patients. These results suggest that BPI may have a place in the treatment of life-threatening infections and conditions associated with bacteremia and endotoxemia. J. Leukoc. Biol. 64: 14–18; 1998.
Transferrin receptor in T cell activation and transplantation
Authors: Bayer Allison L , Baliga Prabhakar , Woodward Jennifer E 
Published: January 2018

Abstract
Transferrin receptor (TfR) expression is up-regulated during T cell activation after the interaction of the T cell receptor with the antigen-major histocompatibility complex and the expression of interleukin-2 (IL-2) receptor. We hypothesize that anti-TfR monoclonal antibody (mAb) will prolong allograft survival by altering T cell responses. In a murine heterotopic nonvascularized cardiac allograft model, CBA/J (H-2k) recipients were transplanted with neonatal C57BL/6 (H-2b) donor hearts. Anti-TfR or isotype-matched control mAbs (100 μg) were administered at the time of transplantation and on the following day. Splenocytes from naive CBA/J mice were stimulated in vitro with C57BL/6 alloantigen. Anti-TfR mAb was administered at 5 μg/mL during the initiation of culture. Cytotoxic T lymphocyte (CTL) and mixed lymphocyte responses (MLR) were performed to assess T cell function. After 24 h in culture, cells were harvested, RNA isolated, and semi-quantitative reverse transcriptase-polymerase chain reaction performed. Anti-TfR mAb prolonged allograft survival to 25.7 ± 0.9 days compared to the isotype control (10.7 ± 0.4 days, P &lt; 0.01, Wilcoxon rank sum). Anti-TfR mAb completely abrogated the CTL response and suppressed the MLR by 70–86% compared to the isotype controls. Anti-TfR mAb suppressed IL-2, interferon-γ (IFN-γ), IL-10, and IL-12 p40 mRNA expression, but had no effect on IL-4, IL-12 p35, and IL-15 mRNA expression. In conclusion, anti-TfR mAb prolongs allograft survival, suppresses T cell function, and alters IL-2, IL-10, IL-12 p40, and IFN-γ mRNA expression. These data suggest that the down-regulation in IL-12 mRNA by anti-TfR mAb may prevent the development of T helper cells, thereby promoting graft survival and altering cell-mediated immune responses. The partial effect by anti-TfR mAb on cytokine mRNA expression may be due to other contributing factors such as costimulation. J. Leukoc. Biol. 64: 19–24; 1998.
Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function
Authors: Howard O M Z , Korte Thomas , Tarasova Nadya I , Grimm Michael , Turpin Jim A , Rice William G , Michejda Christopher J , Blumenthal Robert , Oppenheim J J 
Published: January 2018

Abstract
The intersection of the HIV and the chemokine fields began with the observation that HIV entry into cells could be blocked by certain chemokines. Subsequent work showed that HIV entry is dependent on the presence of specific chemokine receptors. These observations led us to evaluate a series of compounds, ureido analogs of distamycin previously reported to block HIV entry into cells in vitro, for chemokine antagonist activity. One of the distamycin analogs, 2,2′[4,4′-[[aminocarbonyl]amino]bis[N,4′-di[pyrrole-2-carboxamide-1,1′-dimethyl]]-6,8 napthalenedisulfonic acid] hexasodium salt (NSC 651016), is shown here to inhibit syncytia formation and cell fusion. Mechanistic studies showed that this inhibition was not due to conformational changes in gp120-gp41 induced by target cell CD4 and chemokine co-receptor and was therefore not due to interference with binding of HIV-1. Additional mechanistic studies demonstrated that NSC 651016 inhibited chemokine binding to specific chemokine receptors, induced CXCR4 and CCR5 receptor internalization, and inhibited chemokine-induced chemotaxis by macrophage inflammatory protein (MIP)-1α, MIP-1β, RANTES, and stromal-derived factor-1α but not monocyte chemotactic protein-1. Thus, we describe a novel compound that inhibits in vivo replication of HIV-1 by down-regulation of co-receptors. These data lead us to propose that NSC 651016 may have in vivo anti-inflammatory activity. J. Leukoc. Biol. 64: 6–13; 1998.
Regulation of mannose receptor synthesis and turnover in mouse J774 macrophages
Authors: Fiani Maria L , Beitz Jill , Turvy Diane , Blum Janice S , Stahl Philip D 
Published: January 2018

Abstract
The mannose receptor, present on the plasma membrane of macrophages, promotes the internalization of glycoproteins and glycoconjugates via both endocytic and phagocytic pathways. The expression of this receptor is tightly modulated during monocyte/Mφ differentiation and cellular activation. We isolated clonal populations from murine J774 macrophage tumor cells, which differ in their surface expression of functional mannose receptors. To examine the potential mechanisms regulating receptor function in these cell lines, the interaction of receptor with ligand as well as receptor synthesis and degradation was analyzed. J774 clones with both high and low levels of mannose receptor activity were found to synthesize significant amounts of receptor protein, suggesting that the protein may be regulated at the level of synthesis and degradation. In J774 clones expressing very low receptor activity and protein, the half-life of mannose receptor molecules was substantially decreased. The evolution of multiple mechanisms modulating mannose receptor function may be critical in fine-tuning the role of this receptor in antigen processing and in scavenger and host defense functions. J. Leukoc. Biol. 64: 85–91; 1998.
Neutrophil degranulation and phospholipase D activation are enhanced if the Na+/H+ antiport is blocked
Authors: Gewirtz Andrew T , Seetoo Kurt F , Simons Elizabeth R 
Published: January 2018

Abstract
Neutrophils phagocytize high-valency immune complexes (HIC) by an Fc receptor-mediated mechanism. Engaging Fc receptors in this manner induces PMN to generate superoxide and release the contents of both their specific and azurophilic granules. Signaling events that precede and accompany PMN secretion include activation of phospholipase D (PLD), as well as changes in cytoplasmic [Ca2+] (δ[Ca2+]in) and pH (δpHin). Although the role of PLD and δ[Ca2+]in in mediating Fc receptor-mediated PMN secretion has been studied, whether pHin plays a regulatory role has not yet been defined. HIC-stimulated PMN undergo an intracellular acidification followed by a prolonged Na+/H+ antiport-mediated alkalinization. To investigate the role of the pH transient in controlling degranulation, the Na+/H+ antiport was inhibited either with 100 μM dimethylamiloride (DMA) or by substituting N-methyl-glucamine for extracellular sodium. Blocking the antiport with DMA led to hyper-acidified PMN, which exhibited an increase in degranulation, but did not affect generation of superoxide. DMA did not alter the ability of neutrophils to phagocytose and oxidize dichlorodihydrofluoresceinated HIC, suggesting the increase in degranulation was not the result of failed phagocytosis. Investigation into whether the observed increase in degranulation when the antiport was blocked was mediated by PLD or δ[Ca2+]in revealed that blocking the antiport increased HIC-induced PLD activity but had no effect on HIC-induced δ[Ca2+]in. Blocking the Na+/H+ antiport by ion substitution caused similar effects on PMN signaling and secretion as was seen with DMA. These results indicate that Na+/H+ antiport activity is not necessary for degranulation or superoxide release in HIC-stimulated PMN and that hyperacidification of the cytoplasm can modulate degranulation. Therefore, pHin, via its effect on PLD, may be a control point of degranulation and may represent one way that neutrophils achieve differential control of their antibacterial products. J. Leukoc. Biol. 64: 98–103; 1998.
Binding of the endogenously expressed Epstein-Barr virus (EBV) envelope glycoprotein gp350 with the viral receptor masks the major EBV-neutralizing epitope and affects gp350-specific ADCC
Authors: Khyatti Meriem , Ahmad Ali , Blagdon Marie , Frade Raymond , Menezes José 
Published: January 2018

Abstract
The major neutralizing epitope (MNE) for the Epstein-Barr virus (EBV) is present on its envelope glycoprotein gp350/220 (hereafter referred to as gp350) in close proximity to the virus-receptor (CR2) binding site and is recognized by the neutralizing murine monoclonal antibody (mAb) 72A1. We studied the reactivities of 72A1 and another anti-gp350 mAb 2L10 (which does not neutralize EBV) with gp350 expressed on three different lymphoid cell lines (Raji, CEM.NKr and BJA-B). Our results indicate that gp350 expressed on the surface of CR2-positive cells interacts with the viral receptor and that this interaction masks the major EBV-neutralizing epitope. The interaction was reversible and the masked epitope was revealed on incubation with an excess of anti-CR2 mAb OKB7. Gp350-expressing CEM-NKr cells with intact MNE exhibited significantly higher (P ≤ 0.05) lysis in gp350-specific antibody-dependent cellular cytotoxic assays compared with its Raji counterpart. The present results may have important implications for the use of soluble viral receptors as therapeutic agents in acute and chronic EBV and other viral infections (e.g., HIV-1). J. Leukoc. Biol. 64: 192–197; 1998.
Lipopolysaccharide induction of monocyte matrix metalloproteinases is regulated by the tyrosine phosphorylation of cytosolic phospholipase A2
Authors: Shankavaram Uma T , DeWitt David L , Wahl Larry M 
Published: January 2018

Abstract
Activation of human monocytes with lipopolysaccharide (LPS) results in the production of matrix metalloproteinases (MMPs) through a prostaglandin E2 (PGE2)-cAMP-dependent pathway. In this study, the early signaling events involved in this signal transduction pathway were evaluated. Pretreatment of human peripheral blood monocytes with herbimycin A, a tyrosine kinase inhibitor, or arachidonyl trifluoromethyl ketone (AACOCF3), a specific inhibitor of cytosolic phospholipase A2 (cPLA2) inhibited the induction of PGE2 by LPS. This resulted in the inhibition of protein expression of gelatinase B (MMP-9) and interstitial collagenase (MMP-1), two major MMPs secreted by activated monocytes. Addition of arachidonic acid (AA) reversed the inhibitory effect of herbimycin A or AACOCF3 on monocyte MMP production, indicating the importance of tyrosine phosphorylation and the involvement of cPLA2 at an early stage in the signal transduction pathway of MMPs. This finding was further supported by LPS-induced shift in cPLA2 migration and tyrosine phosphorylation based on immunoblotting and immunoprecipitation studies. These results provide evidence that tyrosine phosphorylation of cPLA2 is one of the initial steps needed for the LPS induced MMP production in human monocytes. J. Leukoc. Biol. 64: 221–227; 1998.
Endotoxin activation of mitogen-activated protein kinase in THP-1 cells; diminished activation following endotoxin desensitization
Authors: Durando Mary M , Meier Kathryn E , Cook James A 
Published: January 2018

Abstract
The signal transduction events occurring in monocytes in response to endotoxin (LPS) stimulation are incompletely delineated, although pertussis toxin (PT)-sensitive G proteins and the mitogen-activated protein kinase (MAPK) cascade have been implicated. Cellular desensitization in response to 18-h pre-exposure to 1 μg/mL LPS alters signal transduction pathways of cellular activation and decreases production of certain inflammatory mediators such as thromboxane (Tx)B2, the stable metabolite of TxA2. We hypothesized that LPS stimulation of the human monocyte cell line THP-1 occurs via MAPK activation, and that LPS desensitization, induced by pre-exposure to LPS, is associated with altered signaling through the MAPK cascade. Involvement of a specific MAPK, ERK, in LPS-stimulated TxB2 production was further tested using a specific MAPK cascade inhibitor, PD98059 (PD). PD inhibited LPS and phorbol myristate acetate (PMA)-stimulated ERK activation as demonstrated by immunoblots using anti-activated ERK antibodies. PD significantly inhibited LPS and PMA-stimulated TxB2 synthesis to non-detectable levels, suggesting an involvement of MAPK in LPS-stimulated activation. Because PT-sensitive G proteins mediate LPS-stimulated signal transduction, their role in MAPK activation was tested. Pretreatment with PT inhibited basal and LPS-stimulated, but not PMA-stimulated ERK activation. Activation of ERK after LPS desensitization was also assessed. LPS pre-exposure resulted in a profound decrease in LPS-stimulated activation of ERK, but did not affect PMA activation of ERK. These data implicate the involvement of the MAPK cascade in LPS-stimulated activation of THP-1 cells and suggest coupling of Gi proteins and MAPKs in LPS-stimulated events. LPS desensitization is associated with decreased MAPK activation, but does not impair MAPK activation by PMA. Thus, LPS desensitization appears to selectively alter signal transduction upstream of ERK. J. Leukoc. Biol. 64: 259–264; 1998.
Interferon-γ gene expression in cycling and pregnant mouse uterus: temporal aspects and cellular localization
Authors: Platt J Sue , Hunt Joan S 
Published: January 2018

Abstract
Interferon-γ (IFN-γ) is a potent proinflammatory cytokine that modulates hematopoietic cell maturation, differentiation, activation, and apoptosis. To evaluate the postulate that locally produced IFN-γ could influence uterine hematopoietic cells, specific protein was detected by immunohistochemistry and messenger RNA (mRNA) was identified by in situ hybridization in cycling and pregnant mouse uteri. In cycling uteri, IFN-γ was limited to luminal and glandular epithelial cells during the estrus phase of the cycle. In pregnant uteri, IFN-γ was prominent at early (gestation day 6–10) and late (gestation day 18) stages. IFN-γ-producing cells identified by in situ hybridization included uterine epithelial cells, natural killer cells, macrophages, placental trophoblast cells, and cells in the degenerating metrial gland. Collectively, the data indicate that programming of immune and other cells via autocrine and paracrine pathways could be achieved by locally produced IFN-γ, and suggest that uteroplacental IFN-γ may be most influential during early and late stages of pregnancy. J. Leukoc. Biol. 64: 393–400; 1998.
Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use
Authors: Pizza Francis X , Hernandez Israel J , Tidball James G 
Published: January 2018

Abstract
The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) significantly reduced the concentrations of neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for l-NAME-treated animals compared with water-treated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between l-NAME-treated and control animals, suggesting that l-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells. J. Leukoc. Biol. 64: 427–433; 1998.
Taurine blunts LPS-induced increases in intracellular calcium and TNF-α production by Kupffer cells
Authors: Seabra Vítor , Stachlewitz Robert F , Thurman Ronald G 
Published: January 2018

Abstract
Activation of Kupffer cells by lipopolysaccharide (LPS) plays a pivotal role in the onset of pathophysiological events that occur during endotoxemia and intracellular calcium ([Ca2+]i) is involved in LPS-stimulated cytokine production. Recently, it was shown that Kupffer cells contain a glycine-gated chloride channel. Because taurine, a ubiquitous sulfur-containing β-amino acid, acts similarly to glycine in neurons by causing hyperpolarization, it was hypothesized that taurine would act via a similar mechanism, blunting the LPS-induced increase in [Ca2+]i in Kupffer cells. To test this hypothesis, Kupffer cells were isolated from female Sprague-Dawley rats and cultured for 24 h. LPS-induced changes in [Ca2+]i were monitored fluorometrically in single cells, whereas levels of tumor necrosis factor α (TNF-α) released by Kupffer cells after exposure to LPS were measured by enzyme-linked immunosorbent assay. Taurine significantly blunted the LPS-induced increase in [Ca2+]i in a dose-dependent manner (IC50, 0.1 mM). This effect was reversed by strychnine (1 μM) and was prevented when chloride was removed from the extracellular media. Moreover, taurine increased 36Cl– uptake by Kupffer cells in a dose-dependent manner (EC50, 0.2 mM). Furthermore, strychnine (1 μM) reversed the effect of taurine on 36Cl– uptake. These results indicate that taurine activates a glycine-gated chloride channel in Kupffer cells causing chloride influx. In addition, LPS-induced TNF-α production was reduced by more than 40% by taurine, an effect that was also reversed by strychnine. In conclusion, taurine blocks the increase in [Ca2+]i due to LPS and significantly reduces TNF-α production by mechanisms involving chloride influx into the Kupffer cell. J. Leukoc. Biol. 64: 615–621; 1998.