bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accounting for the peripartum loss of granulated metrial gland cells, a natural killer cell population, from the pregnant mouse uterus
Authors: Delgado Silvia R , McBey Betty-Anne , Yamashiro Shigeto , Fujita Jun , Kiso Yasuo , Croy B Anne 
Published: January 2018

Abstract
Natural killer (NK) cells become a prominent cell population in the rodent uterus during pregnancy. The mature, heavily granulated form of these cells is rare in virgin or postpartum uteri. Death, migration, or dedifferentiation could account for the disappearance of these cells from late gestation uteri. We asked whether uterine NK cells, also known as granulated metrial gland (GMG) cells, die in situ and if expression of Fas antigen is essential for their death. Late in gestation, fragmentation of nuclear DNA was detected histologically by OH-end labeling, as were ultrastructural changes suggesting cell death. NK cells developed in and were lost from the uteri of pregnant Fas antigen-deficient lpr/lpr mice. Postpartum samples of retained placentas contained some residual NK cells that had moved from regions of uterine musculature toward the uterine lumen and were being expelled with the placenta. Thus, both cell death and placental separation remove NK cells from the peripartum uterus.
Activation of alveolar macrophage TNF and MCP-1 expression in vivo by a synthetic peptide of C-reactive protein
Authors: Barna Barbara P , Thomassen Mary Jane , Zhou Ping , Pettay James , Singh-Burgess Sugatha , Deodhar Sharad D 
Published: January 2018

Abstract
Administration of multilamellar vesicles (MLV) encapsulating a synthetic peptide (RS-83277) derived from human C-reactive protein (CRP) augments anti-tumor activity of murine alveolar macrophages and reduces established pulmonary metastases of experimental tumors. To explore mechanisms involved in these phenomena, we investigated cytokine and integrin (CD11b) expression of bronchoalveolar lavage (BAL)-derived alveolar macrophages in control (blank MLV) and RS-83277-MLV-treated C57B1 mice. Alveolar macrophage production of tumor necrosis factor α (TNF-α) and monocyte chemoattractant bioactivity increased at 48 h after treatment with RS-83277-MLV but not control MLV. Chemoattractant activity was neutralized by antibody to monocyte chemoattractant protein-1 (MCP-1), but not irrelevant immunoglobulin G (IgG). Changes were reflected by augmented TNF-α and MCP-1 mRNA levels in pulmonary tissue and enhanced CD11b expression on mononuclear leukocytes derived from total lung tissue, but not on BAL-derived alveolar macrophages. Results suggest that RS-83277-MLV treatment is associated with activation of alveolar macrophage TNF-α and MCP-1 production and up-regulation of adhesion molecules on pulmonary mononuclear leukocytes but not on alveolar macrophages.
Regulation of cytokine gene expression by reactive oxygen and reactive nitrogen intermediates
Authors: Remick Daniel G , Villarete Lorelie 
Published: January 2018

Abstract
Reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI), and cytokines are frequent companions at sites of acute inflammation. Previous work has established a clear link between the production of cytokines and the subsequent generation of ROI and RNI. However, more recent data indicates that ROI and RNI not only serve as end-stage effector molecules of pathogen destruction and tissue injury, but also as initiators of acute inflammation. Specifically, ROI and RNI will up-regulate cytokine gene expression since antioxidants inhibit interleukin 8 (IL-8) production and do not decrease production of other cytokines. Treatment with hydroxyl radical scavengers such as dimethyl sulfoxide (DMSO) will decrease the production of IL-8 in stimulated human whole blood, fibroblasts, type II epithelial cells, and hepatoma cells, but not other cytokines. Addition of exogenous ROI will increase IL-8 production in these same cells. Inhibition of nitric oxide synthase will decrease production of IL-8, whereas addition of nitric oxide (NO)-generating compounds will increase production of IL-8. The hydroxyl radical appears to be the final common pathway of cell activation for IL-8 synthesis, since DMSO will inhibit the NO-driven production of IL-8. Our data indicate that ROI and RNI can serve as intracellular second messengers to induce IL-8 gene expression.
Transcriptional basis for hyporesponsiveness of the human inducible nitric oxide synthase gene to lipopolysaccharide/interferon-γ
Authors: Zhang Xiaoke , Laubach Victor E , Alley Evan W , Edwards Kevin A , Sherman Paula A , Russell Stephen W , Murphy William J 
Published: January 2018

Abstract
The work reported here resolves, at the level of gene regulation, the controversy as to whether or not human monocytes/macrophages can produce nitric oxide (NO) when stimulated with lipopolysaccharide (LPS), with or without co-stimulation by interferon-γ(IFN-γ). Studies included structural comparison of the promoters for human and mouse inducible NO synthase (iNOS) genes, transfection and assay of human and mouse iNOS promoter regions in response to LPS ± IFN-γ, and electrophoretic mobility shift assays of KB response elements. Two explanations for hyporesponsiveness of the human iNOS promoter to LPS ± IFN-γ were found: (1) multiple inactivating nucleotide substitutions in the human counterpart of the enhancer element that has been shown to regulate LPS/IFN-γ-induced expression of the mouse iNOS gene; and (2) an absence of one or more nuclear factors in human macrophages (e.g., an LPS-inducible nuclear factor-κB/Rel complex), that is (are) required for maximal expression of the gene. The importance of resolution of this controversy is that future research in this area should be directed toward the understanding of alternative mechanisms that can result in the successful production of NO.
Bradykinin stimulates phosphoinositide turnover and phospholipase C but not phospholipase D and NADPH oxidase in human neutrophils
Authors: Catz Sergio D , Sterín-Speziale Norma B 
Published: January 2018

Abstract
In response to formyl-Met-Leu-Phe (fMLP), human neutrophils (PMN) generate superoxide anion (O2-) by the enzyme complex NADPH oxidase. The modulation of phosphoinositide (PPI) turnover and the activation of phospholipases C (PLC) and D (PLD) have been shown to be early steps in the oxidative response of fMLP-stimulated PMN. Although the physiological nonapeptide bradykinin (BK) is involved in inflammation, its participation in PMN activation has not been properly studied. In this work, activation of signal transduction pathways that mediate the oxidative response, and the modulation of the NADPH oxidase activity by BK, are analyzed. A direct comparison between the signal transduction pathway induced by BK and fMLP is also made. BK was not able to elicit O2- production by PMN. Nevertheless, several signal transduction pathways associated with PMN activation were triggered by BK. The nonapeptide induced the phosphorylation of prelabeled membrane PPI. This phenomenon was imitated by PMA and inhibited by H7 and staurosporine, thus suggesting the participation of protein kinase c (PKC). A loss of labeled [32P]PPI was triggered by fMLP. The fact that both PMA and fMLP stimulated O2- production but modulated PPI turnover in different ways, indicates that PPI labeling does not correlate with the oxidative response. Because PKC activation seemed to be a prerequisite for BK-induced modulation of PPI turnover, PLC activation could act as an intermediate step in this mechanism. Our results show that BK activated a PIP2-PLC measured as the release of [3H]IP3. On the contrary, a PC-PLD was highly stimulated by fMLP but not by BK. The fact that BK induced PLC activity but neither that of PLD nor NADPH oxidase, whereas fMLP triggered the activation of both phospholipases and evoked the PMN respiratory burst, suggests that diacylglycerol (DAG) from PIP2 as well as PA or PA-derived DAG, synergize to trigger the PMN oxidative response. Finally, BK inhibited O2-production by fMLP-activated PMN in a time-dependent manner. Since BK did not induce NO production by PMN, the inhibitory effect on the oxidative function was not due to ONOO- formation. These data show that BK plays an important role in inflammation by modulating the PMN function.
IL-13 restores an in vitro specific cytolytic response of spleen cells from tumor-bearing rats
Authors: Reisser Danièle , Pinard Dominique , Jeannin Jean-François 
Published: January 2018

Abstract
In a model of colon cancer, spleen cells from tumor-bearing rats are neither cytotoxic nor proliferative in vitro in the presence of tumor cells. Interleukin-13 (IL-13) induced an in vitro cytolytic activity of spleen cells from tumor-bearing rats in response to the tumor they bore, but had no effect on spleen cells from normal rats. This cytotoxic response was dependent on both adherent and nonadherent cells, involving both an antigen-presenting activity that was enhanced by IL-13 and a cytolytic activity of lymphocytes. So, IL-13 reversed the tumor-induced immunosuppression.
Inhibition of neutrophil-endothelial cell adhesion by a neutrophil product, cathepsin G
Authors: Renesto Patricia , Halbwachs-Mecarelli Lise , Bessou Gilles , Balloy V , Chignard Michel 
Published: January 2018

Abstract
In the present study we investigated the modulation of the polymorphonuclear neutrophil (PMN)-endothelial cell adhesion process by the two main proteinases released from activated PMN during their adhesion to endothelium. Our results showed that, in contrast with elastase, cathepsin G was a powerful inhibitor of PMN adhesion to interleukin-1 (IL-1)-treated human umbilical vein endothelial cells. This inhibitory effect was linked to the enzymatic activity of the proteinase and was selectively directed against PMN. Because the viability and the reactivity of PMN were not modified by cathepsin G, we looked for a possible effect on adhesion molecules. L-selectin was not cleaved by cathepsin G, whereas it was by chymotrypsin, a closely related proteinase. Cathepsin G blocked PMN adhesion to activated endothelial cells, but also to serum- or fibrinogen-coated plates, three adhesion processes mediated by GD11b/CD18. However, by FACScan analysis or by immunoprecipitation, we failed to find evidence of modifications of CD11b/CD18 expression. Although the precise molecular target(s) of cathepsin G remain(s) to be defined, these data indicate that this proteinase, which is known as an inflammatory mediator, can also be considered as a potential down-regulator of adhesion reactions involved in the inflammatory process.
Induction of homotypic lymphocyte aggregation: evidence for a novel activation state of the β1 integrin
Authors: Neelamegham Sriram , Simon Scott I , McIntyre Bradley W , Zygourakis Kyriacos 
Published: January 2018

Abstract
Intercellular adhesion of Jurkat lymphocytic cells was investigated by use of monoclonal antibodies 33B6 and 18D3, which bind to the β1 integrin receptor. 33B6 induced homotypic aggregation of Jurkat cells, whereas 18D3 inhibited this aggregation. Jurkat cells could be induced to aggregate at low 33B6 concentrations corresponding to 5% β1 integrin site occupancy, and the rate of aggregation was maximum at 30% occupancy. Simultaneous addition of mAb 18D3 and 33B6 demonstrated that the two antibodies mediate changes in the β1 integrin activation state that are competitive in nature. Aggregation through β1 integrin induced by 33B6 was reversed by subsequent addition of 18D3. To further examine the mechanism by which 33B6 and 18D3 affect cell adhesion function, we explored the binding of monoclonal antibody (mAb) 15/7. This mAb recognizes an activation epitope of the β1 integrin and has been shown to sustain cell adhesion to vascular cell adhesion molecule 1 (VCAM-1) and fibronectin. Activation of Jurkat cells with Mn2+ caused a 2.5-fold increase in 15/7 binding but did not increase binding of 33B6. 33B6 partially blocked 15/7 binding to β1 integrin on unstimulated and Mn2+-activated Jurkat cells. 18D3 did not affect mAb 15/7 binding. These results indicate that 33B6 and 18D3 modulated homotypic aggregation by inducing a novel activation state of the very late activation integrin distinct from the state recognized by 15/7, which supports cell binding to VCAM-1 and fibronectin.
Altered monocyte chemotactic and activating factor gene expression in human glioblastoma cell lines increased their susceptibility to cytotoxicity
Authors: Asano Takeshi , An Taeha , Jia Shu-Fang , Kleinerman Eugenie S 
Published: January 2018

Abstract
A cDNA encoding for human monocyte chemotactic and activating factor (MCAF) was ligated into the retroviral vector pLXSN. These pMCAF-LXSN and antisense p-antiMCAF-LXSN vectors were transfected into HBT20 and HBT28 human brain tumor cells. HBT28 cells constitutively express high amounts of MCAF, whereas HBT20 cells express much less MCAF. HBT20 cells transfected with pMCAF-LXSN (HBT20-MCAF) showed significantly higher MCAF mRNA expression and MCAF protein production than the HBT20-parent or HBT20 cells transfected with control vector (HBT20-LXSN). In contrast, supernatant from HBT28 cells transfected with p-antiMCAF-LXSN (HBT28-antiMCAF) contained less MCAF than HBT28-parent, HBT28-LXSN, and HBT28-MCAF cells. Activated human monocytes killed HBT20-MCAF cells more efficiently compared with HBT20-parent, HBT20-LXSN, and HBT20-antiMCAF cells (P&lt; 0.02), whereas HBT28-antiMCAF cells were killed more efficiently by activated monocytes compared with HBT28-parent, HBT28-LXSN, and HBT28-MCAF cells (P&lt; 0.05). Cultured supernatants from activated monocytes plus HBT20-MCAF cells or from activated monocytes plus HBT28-antiMCAF cells inhibited the growth of HBT20 and HBT28 cells, respectively. Altered MCAF expression can therefore enhance the ability of activated monocytes to kill brain tumor cells. This increased cytotoxicity is partially dependent upon the basal state of MCAF in the individual tumor cells.
The heavy metal lead modulates the expression of both TNF-α and TNF-α receptors in lipopolysaccharide-activated human peripheral blood mononuclear cells
Authors: Guo Tai Liang , Mudzinski Stanley P , Lawrence David A 
Published: January 2018

Abstract
It has been shown that lead (Pb) potentiates lipopolysaccharide (LPS) lethality in animals by increasing the secretion and uptake or reactivity of tumor necrosis factor-α (TNF-α). Herein we report that PbCl2 increased TNF-α secretion from LPS-treated human peripheral blood mononuclear cells (PBMC) in a concentration- and time-dependent manner. PbCl2 also increased total cellular TNF-α levels but had no effect on the steady-state levels of TNF-α mRNA. PbCl2 decreased membrane-associated TNF-α (mTNF-α) on LPS-treated monocytes, whereas PbCl2 increased TNF-α receptor (TNF-R) p55 surface expression, and had no effect on TNF-R p75 surface expression by LPS-treated monocytes. Overall, the results suggest that PbCl2 increases TNF-α expression by posttranscriptional mechanisms in human PBMC, and enhances the reactivity and uptake of TNF-α by increasing the surface expression of TNF-R p55.
The role of early growth response gene 1 (egr-1) in regulation of the immune response
Authors: McMahon Steven B , Monroe John G 
Published: January 2018

Abstract
The induction of immediate early genes in cells of the immune system is critical to determining the ultimate outcome of exposure to antigen. The importance of many of these genes relates to the role their transcription factor products play in dictating patterns of expression of downstream, function-related genes. Evidence from several systems indicates that the immediate early gene, egr-1 may be of particular importance in the immune system. Recently, the egr-1 promoter has been shown to be highly responsive to the diverse biochemical signals generated by antigen and cytokines in cells of the immune system. Furthermore, an important role for egr-1 in determining the differentiation pathway of myeloid cell precursors has been recently elaborated. Finally, potential targets of regulation by the zinc-finger transcription factor encoded by egr-1 include the interleukin-2, CD44, ICAM-1, and tumor necrosis factor genes. The role of egr-1 in regulation of the immune response will be discussed in the context of these recent studies.
Anti-CD69 antibodies enhance phorbol-dependent glucose metabolism and Ca2+ levels in human thymocytes. Antagonist effect of cyclosporin A
Authors: Conde M , Montaño R , Moreno-Aurioles V R , Ramirez R , Sanchez-Mateos P , Sanchez-Madrid F , Sobrino F 
Published: January 2018

Abstract
The human activation antigen CD69 is an early inducible surface glycoprotein acquired by T cells in the thymus at the stage of positive selection and during activation of mature lymphoid cells both in vivo and in vitro. We have studied the regulatory influence of CD69 activation pathway on the glycolytic process and transduction signals of thymocytes. Treatment of human thymocytes with different anti-CD69 monoclonal antibodies (mAbs), in the presence of submitogenic doses of phorbol ester, produced an enhanced release of lactate without significant alterations in Fru 2,6-P2 levels or phosphofructokinase-2 (PFK-2) and pyruvate kinase activities. A small increase in phosphofructokinase-1 (PFK-1) activity was also detected. Furthemore, anti-CD69 mAb increased the glucose detritiation from [2-3H] and [3-3H]glucose, thus indicating an enhanced flux through hexokinase and PFK-1 steps. In addition, de novo synthesis of diacylglycerol and intracellular Ca2+ levels increased after anti-CD69 mAb treatment. The stimulatory effects of anti-CD69 mAb on both glycolysis and Ca2+ levels were inhibited by cyclosporin A. Because CD69 molecules are present in certain subset populations of immature thymocytes, the ability of anti-CD69 mAb to stimulate the glycolysis, the synthesis of diacylglycerol and the intracellular Ca2+ levels suggest that the activation signals delivered through CD69 molecules could play a role in the thymus cells maturation.
Glycated serum albumin induces chemokine gene expression in human retinal pigment epithelial cells
Authors: Bian Zong-Mei , Elner Susan G , Strieter Robert M , Glass Mary B , Lukacs Nicholas W , Kunkel Steven L , Elner Victor M 
Published: January 2018

Abstract
Chronic hyperglycemia is thought to be important in the development of diabetic neovascularization but the mechanisms involved remain poorly understood. Interleukin-8 (IL-8) is a leukocyte chemokine and activating agent with angiogenic properties that is present in diabetic vitreous and may play a role in diabetic vasculopathy. We studied IL-8 and monocyte chemotactic protein-1 (MCP-1) production by human retinal pigment epithelial (hRPE) cells exposed to glycated human serum albumin (GHSA). Enzyme-linked immunoassay GHSA (500 μg/mL)-treated hRPE cells secreted levels of IL-8 and MCP-1 detectable within 4 h and reached 26.0 ± 1.3 and 42.2 ± 0.4 ng/106 cells/mL after 24 h, respectively. Induction of IL-8 and MCP-1 by GHSA at concentrations ranging from 62.5 to 3,000 μg/mL exhibited dose-dependent kinetics. The GHSA-induced chemokine secretion by hRPE was almost completely inhibited by actinomycin D and cycloheximide, suggesting that de novo mRNA and protein synthesis are necessary for the GHSA-induced IL-8 and MCP-1 production. Northern blot analysis of GHSA-induced hRPE IL-8 and MCP-1 mRNA expression corresponded to the time- and dose-dependent increases measured by enzyme-linked immunosorbent assay. High concentrations of glucose (20 mM; 360 mg/dl) increased GHSA-induced hRPE IL-8 and MCP-1 secretion, whereas added insulin (0.5 ng/mL) inhibited IL-8 but not MCP-1 protein secretion and mRNA expression. GHSA also induced hRPE to secrete GRO-α, RAN-TES, and NAP-2 chemokines. GHSA induction of hRPE chemokines further suggests a role for the hRPE in leukocyte infiltration, vascular injury, and neovascularization.
Expression of the activated (Y501-F501) hck tyrosine kinase in 32Dcl3 myeloid cells prolongs survival in the absence of IL-3 and blocks granulocytic differentiation in response to G-CSF
Authors: English B Keith 
Published: January 2018

Abstract
The hematopoietic cell kinase (hck), a member of the src family of intracellular, membrane-associated protein tyrosine kinases, is primarily expressed in mature granulocytes and monocyte/macrophages.
The use of chimeric human Fcε receptor I to redirect cytotoxic T lymphocytes to tumors
Authors: Kershaw Michael H , Darcy Phillip K , Trapani Joseph A , Smyth Mark J 
Published: January 2018

Abstract
Chimeric receptors that redirect effector cell function to tumor cells or virus-infected cells have received much attention. Given the high affinity of FcRI for immunoglobulin E (IgE) and low serum IgE levels, redirection of effector cells using Fc receptor may provide a novel, versatile, and effective anti-tumor strategy. We have used a mouse perforin 5'-promoter to express a single-chain human Fc receptor in the mouse cytotoxic T lymphocyte cell line, CTLL-R8. Upon ligation of the chimeric Fc receptors by IgE, a signal for effector function is transmitted via the intracellular domain of CD3. Selection in G418-contaming medium produced CTLL-R8 transfectant clones that: (1) expressed chimeric Fc receptor as determined by flow cytometry; (2) bound human IgE antibodies with high affinity as determined by Scatchard analysis; (3) specifically rosetted IgE-coated SRBC; (4) lysed target cells in IgE-mediated ADCC and reverse ADCC assays; and (5) retarded tumor growth in a Winn assay. Therefore these chimeric Fc receptors can effectively redirect cytotoxicity to tumor cells. Future efforts will assess the versatility and efficacy of these IgE-binding chimeric receptors to redirect killer cell function in animal tumor models.
Dynamic imaging of neutrophil migration in three dimensions: mechanical interactions between cells and matrix
Authors: Mandeville John T H , Lawson Moira A , Maxfield Frederick R 
Published: January 2018

Abstract
Fluorescence confocal microscopy was used to obtain three-dimensional (3-D) images of human neutrophils migrating through a 3-D matrix of amniotic membrane with a temporal resolution of 30–60 s and a spatial resolution of 2 μm in the z-dimension. Neutrophils migrating in response to a chemoattractant gradient within a 3-D matrix were apparently able to generate traction by use of lateral pseudopods inserted into footholds in the matrix as evidenced by matrix distortion. Similar anchored pseudopods were seen in cells migrating across polycarbonate membranes with 0.8-μm pores; the presence of these pores increased cell polarization and migration compared with cells on membranes without pores. Expansion of pseudopods distal to narrow constrictions in the matrix and porous filters was observed and appeared to be used to pull cells through the openings. Neutrophils deformed parts of the elastic amnion matrix during migration without permanently altering the substrate. Contact guidance of neutrophils crawling along matrix fibrils was also observed. These observations show that neutrophils migrating in 3-D are able to utilize mechanical structures in the matrix, not present on 2-D surfaces, to generate traction for locomotion.