bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of granulocyte-macrophage colony-stimulating factor on myeloid cells and its clinical applications
Authors: Hill Arnold D K , Naama Hassan A , Calvano Steve E , Daly John M 
Published: January 2018

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a naturally occurring growth factor produced by several cell types in response to a variety of stimuli. GM-CSF has potent stimulatory effects on the growth and maturation of hematopoietic cells and has profound effects on mature circulating effector cells. Clinical applications of GM-CSF include ameliorating chemotherapy-induced neutropenia and enhancing hematopoietic recovery after bone marrow transplantation. This review evaluates the effect of GM-CSF on myeloid cells and its clinical applications.
Induction of apoptotic cell death in mouse lymphoma and human leukemia cell lines by a calcium-binding protein complex, calprotectin, derived from inflammatory peritoneal exudate cells
Authors: Yui Satoru , Mikami Masaaki , Yamazaki Masatoshi 
Published: January 2018

Abstract
We have previously shown that the calcium-binding protein complex, calprotectin, purified from rat inflammatory peritoneal cells exerts marked cytotoxic activity against rat, mouse, and human tumor cells. We studied here whether the cytotoxicity is caused by induction of apoptosis, using mouse EL-4 lymphoma and human MOLT-4 leukemia lines as targets. The rat calprotectin sample inhibited [3H]thymidine incorporation into these cells by partially 24 h and almost completely in 48 h of culture at concentrations of 100–200 μg/ml. Morphological changes, that is, loss of cell volume and nuclear condensation and/or fragmentation, appeared in both cell types cultured with calprotectin from 20 h, and such apoptotic cells subsequently increased in number to compose the great majority of the cells at 40 h. Cell death, measured by stainability with trypan blue, lagged behind the emergence of the apoptotic morphology by about 2 and 10 h in EL-4 and MOLT-4 cells, respectively. DNA fragmentation was observed in EL-4 cells cultured with calprotectin, whereas it was not observed in MOLT-4 cells, consistent with results of flow cytometry showing that loss of cell DNA content caused by the factor was greater in EL-4 cells. The data indicate that calprotectin induces the apoptosis of certain tumor cells but that the occurrence of DNA fragmentation is dependent on cell type. Finally, the apoptosis-inducing activity of the calprotectin sample was abrogated by the presence of 10 μM zinc, whereas it was not affected by 5 mM calcium or magnesium.
Effect of recombinant human macrophage-colony stimulating factor on marrow, splenic, and peripheral hematopoietic progenitor cells in mice
Authors: Yamauchi Takeshi , Yada Kouji , Umemura Akio , Asakura Eiji , Hanamura Takuji , Tanabe Toshizumi 
Published: January 2018

Abstract
The effects of human macrophage colony-stimulating factor (M-CSF) on marrow, splenic, and peripheral progenitor cells (CFU-M, CFU-GM, and CFU-G) were investigated in mice administered recombinant human M-CSF (8-4,000 μg/kg). Single injection of 4,000 μg/kg of M-CSF resulted in a decrease in the number of marrow progenitor cells (CFU-M, CFU-GM, and CFU-G) on day 2 followed by a gradual increase, returning to the original level on day 4 or 5. In contrast, each type of splenic progenitors tested for started to increase markedly on day 2, reaching a level 4- to 15-fold higher than that of the basal value on day 3 or 4. Peripheral CFU-M, CFU-GM, and CFU-G also increased on day 2. In addition, administration of 800 μg/kg of M-CSF in mice caused a decrease in marrow CFU-G, as well as an increase in splenic CFU-G. The present results indicate that treatments of mice with pharmacological concentrations of human M-CSF affect the number of progenitor cells not only of monocyte/macrophage lineage but also of granulocyte lineage. Also, the coincidence between decrease of marrow progenitor cells and increase of splenic and peripheral progenitor cells suggests that the progenitor cells are released from bone marrow to peripheral blood and reseeded to the spleen by the action of M-CSF.
Examination of the mononuclear phagocyte system in lupus-prone male BXSB mice
Authors: Vieten G , Grams B , Müller M , Hartung K , Emmendörffer A 
Published: January 2018

Abstract
During the course of lupus-like autoimmune disease male BXSB mice develop an increasing monocytosis in the peripheral blood. As we demonstrated previously, this monocytosis is parallelled by an expansion of a strain-specific high number of macrophage precursor cells (CFU-M) in the bone marrow of male mice. To test the hypothesis that the expanded mononuclear phagocyte system (MPS) may promote autoimmune disease in these mice the organ-associated macrophage system was examined. Our latest data show that an unusual expansion of CFU-M also appears in spleen and liver of male mice 2 weeks after birth. In addition to a morphological alteration of the organs during the course of the disease there is a change in number and distribution of organ-resident macrophages. Considering these results the possible contribution of the expanded MPS in promoting autoimmune disease is discussed.
Soluble extracellular antigen-specific T cell immunoproteins
Authors: Cone Robert E 
Published: January 2018

Abstract
Some T cells release proteins that bind specifically to antigens that have not been processed by antigen-presenting cells. These soluble immunoproteins induce or effect antigen-specific T cell functions in immunoregulation and/or hypersensitivity. After certain immunization regimens, T cell immunoproteins specific for the immunogen rise in serum, and therefore may be an antigen-specific, humoral manifestation of the activation of some T cells during an immune response. Although non-MHC (major histocompatibility complex)-associated antigen is bound, soluble antigen-specific T cell immunoproteins share variable and constant region epitopes and some amino acid sequence with the T cell receptor for antigen α or β chains, and their expression depends on T cell receptor structural genes. Herein, the properties of extracellular antigen-specific T cell immunoproteins are reviewed and it is suggested that these molecules are a soluble analogue of the T cell receptor for antigen and provide an amplifying element for some T cell functions.
Augmentations of glucose uptake and glucose transporter-1 in macrophages following thermal injury and sepsis in mice
Authors: Gamelli Richard L , Liu Hong , He Li-Ke , Hofmann Cecilia A 
Published: January 2018

Abstract
Glucose is the primary metabolic substrate of macrophages, which are critical components of the host response to injury and infection. We have carried out a series of studies to examine macrophage glucose uptake and the status of glucose transporter 1 (GLUTI) at both the mRNA and protein level. Peritoneal macrophages that were obtained from mice undergoing sham burned (S), 15%TBSA burn (B)±Pseudomonas aeruginosa burn infection (B + I) and lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) administration. [3H]deoxyglucose uptake was significantly increased (B, 157 ± 9%; B + I, 243 ± 19%; S + LPS, 231 ± 24%; S + TNF-α, 379 ± 18%; B + LPS, 230 ± 13%; and B + TNF, 305 ± 23%, P &lt; 0.01 vs. sham). GLUTI mRNA and protein levels were increased as well (mRNA: B, 135 ± 13%; B + I, 250 ± 33%; S + LPS, 282 ± 29%; S + TNF-α, 193 ± 19%; B + LPS, 378 ± 20%; and B + TNF-α, 204 ± 16%; protein: B, 159 ± 27%; B + I, 181 ± 17%; S + LPS, 219 ± 26%; S + TNF-α, 343 ± 51%; B + LPS, 366 ± 41%; and B + TNF-α, 415 ± 44, P&lt; 0.01 vs. sham). Macrophages co-cultured with LPS or TNF-α in vitro demonstrated a similar response pattern. Following burn injury and infection, macrophages augment their cellular glucose uptake, which is facilitated by an increased GLUT1 mRNA and protein levels. TNF-α elicited by LPS may mediate this enhanced carbohydrate metabolism at the point of glucose entry into the cell.
IFN-α-mediated suppression of low-affinity Fc receptors on Peyer’s patch lymphocytes and augmentation of soluble CD23: implications for IgE responses
Authors: Miller Hanan , Bluth Martin H , Chice Seto M , Durkin Helen G , Auci Dominick L 
Published: January 2018

Abstract
The ability of interleukin (IL)-6 or interferon-α (IFN-α) to regulate expression of low-affinity Fc receptor (CD23) and serum levels of CD23 was studied in benzylpenicilloyl-keyhole limpet hemocyanin-sensitized BALB/c mice at the peak of a haptenspecific immunoglobulin E (IgE) antibody-forming cell (AFC) response. These responses are analogous to those observed in human atopic disease. To induce peak IgE responses, mice were injected intraperitoneally with BPO-KLH (10 μg) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected subcutaneously with IL-6 (100-1000 U) or IFN-α (1000-10,000 U). On day 46, numbers of CD23+ lymphocytes in Peyer’s patches (PP), mesenteric lymph nodes (MLN), and spleen and levels of soluble CD23 in serum were determined (flow microfluorimetry and enzyme-linked immunosorbent assay, confirmed by competition assay). Data are expressed as percent total cells or as optical density at 490 nm. IFN-α treatment strongly suppressed (up to 100%) numbers of CD23+ cells exclusively in PP (i.e., numbers of CD23+ cells in MLN and spleen were unchanged) whereas serum levels of soluble CD23 were dramatically increased (60%). IL-6 treatment had no effect on either numbers of CD23+ lymphocytes or on serum levels of soluble CD23. The data suggest that the mechanism(s) by which IFN-α, but not IL-6, regulates IgE responses involves suppression of CD23 expression on lymphocytes in PPs and supports a central role for these organs in regulation of IgE responses in vivo.
Okadaic acid inhibits the signal responsible for activation of the NADPH-oxidase in neutrophils stimulated with serum-opsonized yeast
Authors: Harbecke Olle , Lundqvist Helen , Dahlgren Claes 
Published: January 2018

Abstract
The effects of the phosphatase inhibitor okadaic acid (OA) on human neutrophil phagocytic activity were investigated. The chemiluminescence response was found to be greatly reduced in OA-treated neutrophils during phagocytosis of serum opsonized yeast particles in comparison to control cells. However, the OA-treated neutrophils phagocytosed yeast particles to the same extent as control cells and the engulfment of the prey was accompanied by phagolysosomal formation in both OA- treated and nontreated cells. We thus found that the OA effect was selective in the sense that it inhibits the NADPH-oxidase activity in neutrophils phagocytosing yeast particles but not uptake of the prey or phagolysosomal formation. Based on the fact that the NADPH-oxidase activity induced by the chemoattractant formyl-methionyl-leucyl-phenylalanine was not reduced but elevated in OA-treated neutrophils, we conclude that the state of phosphorylation has no direct effect on the oxidase, but is of importance for the NADPH-oxidase activating signal(s) generated during phagocytosis of the yeast particles.
Membrane phospholipid asymmetry: host response to the externalization of phosphatidylserine
Authors: Bruckheimer Elizabeth M , Schroit Alan J 
Published: January 2018

Abstract
Membrane phospholipid asymmetry is an important regulator of cellular function and homeostasis. The activities of lipid transporters are contributing factors to the regulation of membrane lipid composition over the lifespan of the cell. Alterations in the activites of these proteins result in the movement of phosphatidylserine to the cell’s outer leaflet. This promotes several physiologic responses including initiation of the coagulation cascade and cell recognition by the reticuloendothelial system.
Enhanced expression and production of monocyte chemoattractant protein-1 in inflammatory bowel disease mucosa
Authors: Grimm Michael C , Elsbury Sue K O , Pavli Paul , Doe William F 
Published: January 2018

Abstract
Peripheral blood monocytes are recruited to the inflamed mucosa of inflammatory bowel disease but the specific chemotactic signals responsible for their attraction are not known. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine with potent monocyte attracting and activating properties and the aim of this study was to examine its expression and production in inflammatory bowel disease. In situ hybridisation demonstrated mRNA for MCP-1 in macrophages, some of which had been recently recruited from the circulation as demonstrated by their co-expression of the monocyte marker CD14, as well as in smooth muscle and endothelial cells in inflamed mucosa. Immuno-histochemical studies showed a corresponding distribution of MCP-1 protein production by macrophages, smooth muscle, and endothelial cells. By contrast minimal MCP-1 mRNA expression and protein were found in histologically normal mucosa. Macrophages isolated from surgically resected inflammatory bowel disease colons and examined by Northern analysis expressed MCP-1 mRNA significantly more frequently (15/24 vs. 0/19, P&lt; 0.0001) than macrophages from histologically normal mucosa from colon cancer resections. Blood monocytes stimulated by lipopolysaccharide and treated with hydrocortisone, 5-aminosalicylic acid, or cyclosporin A showed reduced MCP-1 expression and production in the presence of these agents. This study demonstrates increased expression of MCP-1 mRNA and protein and cells of origin of MCP-1 in inflamed intestinal mucosa. Together with the demonstrated influence of therapeutic agents on monocyte MCP-1 production the findings suggest a role for MCP-1 in monocyte attraction to the mucosal lesion of inflammatory bowel disease.
Colony stimulating factor-1 expression is developmentally regulated in the mouse
Authors: Roth Philip , Stanley E Richard 
Published: January 2018

Abstract
Colony stimulating factor-1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. To determine whether CSF-1 plays a role in the perinatal development of these cells, CSF-1 protein and mRNA expression in tissues and serum from fetal/neonatal mice and their mothers was analyzed. As fetal/neonatal age increased, CSF-1 concentrations rose in liver, kidney, and lung, declined in brain and serum, and did not change in intestine and heart. Concurrently, fetal/neonatal CSF-1 concentrations were higher in liver, kidney, and serum and lower in lung, brain, intestine, and heart than maternal tissue/serum concentrations, which showed no correlations with gestational or post-partum stage. CSF-1 mRNA was detected in all tissues examined and its expression increased in lung and heart and decreased in brain with increasing fetal/neonatal age. The developmental regulation of mouse CSF-1 expression appears to be important for mononuclear phagocyte development during this period.
The inflammatory macrophage response to MCMV in mice with a retroviral immunodeficiency syndrome (MAIDS)
Authors: Allcock Richard J N , Peacock Craig D , Price Patricia 
Published: January 2018

Abstract
We have shown that normal C57BL/6J mice are moderately resistant to infection with murine cytomegalovirus (MCMV) and that this resistance is impaired by prior infection with LP-BM5 MuLV, which causes a disease (MAIDS) similar to early HIV-induced disease. This study investigates macrophage function in MAIDS+ mice challenged with MCMV. MAIDS reduces the influx of cells into the peritoneal cavity seen in normal C57BL/6J mice 6 days after MCMV infection. The infiltrates contained cells that resembled activated macrophages, as they took up colloidal gold, expressed the macrophage marker Mac-1, had high levels of acid phosphatase activity, and were lymphocytostatic when co-cultured with activated T cells. MAIDS+ mice had a higher percentage of cells able to take up colloidal gold and higher acid phosphatase activity per cell. The cells were also more lymphocytostatic and produced higher levels of interleukin-1 and tumor necrosis factor-α on days 4 and 6 after MCMV infection. Hence, MAIDS enhances baseline and induced macrophage activity, but depresses infiltration into the site of inflammation.
Lysis of leukemic cells by human macrophages: inhibition by 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor
Authors: Nakabo Yukiharu , Pabst Michael J 
Published: January 2018

Abstract
Proteases are known to be involved in regulation of macrophage activation and killing. We examined the effect of a serine protease inhibitor, 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), on lysis of leukemic cells by human macrophages. Monocytes, isolated by Histopaque gradients and centrifugal elutriation, were cultured for 5 days in RPMI-1640 medium with 5% AB serum, and then activated with interferon-γ (IFN-γ; 100 U/mL) and lipopolysaccharide (LPS) (5 ng/mL), with or without AEBSF, for 2 days. On day 7, macrophages were washed, fresh medium without AEBSF added, and target cells added for 2 days. Lytic activity against two leukemic cell lines (K562 and HL-60) was assessed by an 111indium-releasing assay. Macrophages treated with IFN-γ + LPS lysed K562 and HL-60 cells. AEBSF (50–150 μM) blocked the killing of these leukemic cells in a concentration-dependent manner. Other protease inhibitors were not effective. AEBSF was nontoxic at the concentrations used, and did not inhibit tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion from the macrophages. The lytic activity against leukemic cells was inhibited by anti-TNF-α antibody, but not by anti-IL-1β, nor by superoxide dismutase or catalase. However, the leukemic cells were resistant to being killed by recombinant TNF-α alone in the absence of macrophages, indicating that TNF-α was required for killing, but that other factors that were inhibited by AEBSF were also required. Serum-free culture supernatant of activated macrophages had significant cytotoxic activity against leukemic cells. This cytotoxic activity was not altered by addition of AEBSF to the culture supernatant, suggesting that AEBSF affected macrophage activation, rather than inhibiting cytotoxic proteases secreted by the macrophages, or affecting the target cells themselves. Thus, a protease, which is susceptible to AEBSF, might be involved in the activation of macrophages, and might regulate the secretion of antitumor effector molecules other than TNF-α.
Effects of hepatocellular mitogens on cytokine-induced nitric oxide synthesis in human hepatocytes
Authors: Liu Zhi-Ze , Cui Shijun , Billiar Timothy R , Dorko Kenneth , Halfter Willi , Geller David A , Michalopoulos George , Beger Hans-G , Albina Jorge , Nussler Andreas K 
Published: January 2018

Abstract
The synthesis of induced nitric oxide (NO) is regulated by several cytokines, including growth factors produced following hepatic injury and inflammation. However, little information is available on the role of growth factors in regulating the inducible NO synthase in human hepatocytes. The capacity of hepatocellular mitogens (HGF, EGF, and TGF-α) to regulate the inducible NO synthase (iNOS) was studied in human hepatocytes incubated with inflammatory cytokines and lipopolysaccharide (LPS). Furthermore, the effects of hepatic mitogens on NO-induced changes in DNA and protein synthesis was studied. It was found that NO-mediated decrease of protein and DNA synthesis were partially reversed by the mitogens. This was associated with a down-regulation in cytokine-mediated hepatocyte NO formation, iNOS mRNA expression, and NOS enzyme activity. Cytokine-induced NO formation or SNAP, an NO donor, added with cytokines increased hepatocyte chromatin condensation but no DNA fragmentation was observed. The increase in chromatin condensation was partially reversed by hepatic mitogens and corresponded with the inhibition of NO production. Thus, the hepatic mitogens, HGF, EGF, and TGF-α, all suppress iNOS expression and it is the suppression of iNOS that appears to be responsible for the mitogen-reduced preservation of DNA and protein synthesis and prevention of chromatin condensation.
T cell activation via the disialoganglioside GD3: analysis of signal transduction
Authors: Ortaldo John R , Mason Anna T , Longo Dan L , Beckwith Margaret , Creekmore Stephen P , McVicar Daniel W 
Published: January 2018

Abstract
The monoclonal antibody (mAb) R24 is a murine immunoglobulin G3 (IgG3) that reacts with the GD3 disialoganglioside present on melanoma cells as well as a subset of T cells. R24 mAb has induced antitumor responses both alone and in combination with interleukin-2 (IL-2) in clinical trials. We have reported T cell activation via GD3 as measured by the induction of tyrosine phosphorylation. In this study a more detailed analysis of signal transduction after ligation of GD3 was performed in an attempt to understand the mechanism of in vivo therapeutic benefits observed. Analysis of subsequent events indicated that GD3 engagement resulted in phospholipase Cγ phosphorylation and calcium flux. When ras-associated events were examined, GD3 signaling resulted in ras activation as determined by GDP/GTP conversion as well as dose-and time-dependent IP3 activation. In addition, the majority of the IPS activation by GD3 was inhibited by herbimycin A pretreatment. Elucidation of the nature and potential role of this moiety in GD3 signal transduction should be useful. Collectively, these data suggest a novel mechanism of T cell activation via a single, non-protein, surface moiety. This novel form of T cell-mediated activation may permit the delivery and local activation of effector cells at the tumor resulting in site-specific activation of the immune system.
Secretory phospholipase A2 activity is elevated in bronchoalveolar lavage fluid after ovalbumin sensitization of guinea pigs
Authors: Sane Aneysa C , Mendenhall Tiffany , Bass David A 
Published: January 2018

Abstract
Arachidonic acid (AA), the precursor of eicosanoids, is released from the sn-2 position of phospholipids by both secretory (8PLA2) and cytosolic phospholipase A2 (CPLA2). Eicosanoids have been shown to contribute to bronchospasm in asthma. We measured the enzymatic activity of 8PLA2 and CPLA2 in the bronchoalveolar lavage fluid and cells, respectively, in male Hartley guinea pigs sensitized with ovalbumin. sPLA2 activity was also measured from alveolar macrophages (AM) in culture from unsensitized and sensitized animals. There was an increase in 8PLA2 activity and AA content in the lavage fluid following sensitization (18.73 ± 1.33 to 25.74 ± 3.22% hydrolysis and 17.97 ± 12.39 to 44.76 ± 13.37 pmol AA/mL BAL, mean ± SD), which remained elevated but without further increase 4 or 24 h after antigen challenge. AM from unsensitized and sensitized-unchallenged animals did not secrete 8PLA2 activity in culture for 3 h and therefore do not appear to be the cell source of the sPLA2 activity present in the alveolar lavage fluid following OA sensitization. In contrast to the increase in 8PLA2 in lung lavage fluid, Western blotting for CPLA2 from lung lavage cells showed no increase 4 or 24 h after antigen challenge compared with sensitization alone. CPLA2 enzymatic activity of the cytosol fraction of lung lavage cells showed no changes with antigen sensitization or challenge. In summary, intraperitoneal sensitization with ovalbumin in male Hartley guinea pigs caused an increase in both sPLA2 and AA in bronchoalveolar lavage fluid without a need for antigen challenge. The increased 8PLA2 enzymatic activity following sensitization may be responsible for the elevation of AA in the bronchoalveolar lavage fluid observed after antigen sensitization.