bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Pulmonary Macrophages in Resistance to Experimental Metastasis
Authors: Jackson R A , Lill P H , Gangemi J D 
Published: January 2018

Abstract
Intranasal inoculation of C3H/HeN mice with Propionibacterium acnes activates pulmonary macrophages but not splenic or peritoneal macrophages. When mice so treated were injected IV with tumor cells, no protection against the challenge was seen. Conversely, inoculation of C3H/HeN mice with P. acnes by the IP route activated splenic and peritoneal macrophages but not pulmonary macrophages. When mice with activated splenic and peritoneal macrophages were challenged with an IV injection of tumor cells, the mice demonstrated an increased resistance to the formation of pulmonary tumors. Thus, activation of splenic and peritoneal macrophages correlated better with protection against IV tumor challenge than activation of pulmonary macrophages. Experiments were done that demonstrated that the effect was not due to the augmentation of NK cell activity.
The data are consistent with the conclusion that activated pulmonary macrophages alone are not effective in conferring resistance to pulmonary tumor nodule formation in this tumor model.
Biochemical Analysis and Biological Activities of Immunoaffinity Purified Natural Murine Gamma Interferon (MuIFN-γ)
Authors: Greenfield Robert S , Kiener Peter A , Chin David P , Curry Robert C , Spitalny George L 
Published: January 2018

Abstract
A rapid one-step procedure for the purification of natural murine gamma interferon (MuIFN-γ) by immunoaffinity chromatography has been developed. Crude MuIFN-γ was passed through a column containing immobilized anti-MuIFN-γ monoclonal antibody, and the column was washed with high salt and detergent. Active MuIFN-γ was subsequently eluted with ammonium thiocyanate/glycerol (yields of 20-40%). Analysis of the immunopurified interferon by sodium dodecyl sulfate Polyacrylamide gel electrophoresis under reducing conditions revealed biologically active bands of about 19.5, and 14 kd. Under nonreducing conditions, three active bands at 35, 19.5, and 14 kd could be seen. Gel filtration of the immunopurified MuIFN-γ under reducing or nonreducing conditions showed a single major peak of antiviral activity corresponding to a molecular weight of 43 kd. The protein eluted from each band from the SDS-gel, in addition to possessing antiviral activity, was shown to activate macrophages in three assays: a) macrophage tumoricidal activity, b) hydrogen peroxide secretion, and c) expression of la antigen on the surface of exudate macrophages.
Two-Dimensional and Three-Dimensional Movement of Human Polymorphonuclear Leukocytes: Two Fundamentally Different Mechanisms of Location
Authors: Schmalstieg Frank C , Rudloff Helen E , Hiliman Gilbert R , Anderson Donald C 
Published: January 2018

Abstract
Patients with an inherited deficiency of the adherence glycoproteins LFA-1, Mac-1, and p150,95 are unable to mobilize polymorphonuclear leukocytes (PMNLs) to peripheral sites of inflammation. LFA-1/Mac-1/p150,95-deficient PMNL exhibited profoundly impaired movement stimulated by chemotactic factors when the cells were required to move over two-dimensional surfaces. Less impairment of movement was demonstrated in three-dimensional movement through cellulose filters. A possible explanation for this difference in cell translational mobility is that movement in cellulose filters is less adherence dependent than movement over a two-dimensional plastic surface. Movement of PMNL in collagen gels is known to be relatively independent of adherence. No deficiency of translational mobility of PMNL from LFA-1/Mac-1/p 150,95-deficient patients was observed in collagen gels. Antibodies against the common beta subunit effectively blocked two-dimensional movement but had little effect on three-dimensional movement through cellulose filters or collagen gel matrices. HL-60 cells were employed as a model to investigate the effects of adherence on cell movement. Treatment of HL-60 cells with phorbol myristate acetate resulted in the appearance of Mac-1 and p150,95 on the cell surface. Concurrently, the cells exhibited increased adherence to glass and plastic. In spite of increased adherence, HL-60 cells showed no translational movement, indicating factors other than the ability to adhere were important in cell motility. These experiments implied that PMNLs undergo two fundamentally different kinds of motion, one adherence dependent (two-dimensional movement) and the other largely adherence independent (three-dimensional movement). These findings are consistent with the view that egress of PMNLs from the vascular space is adherence dependent. Movement through extravascular tissues may be adherence independent.
Comparison of Five Short-Term Assays That Measure Nonspecific Cytotoxicity Mediated to Tumor Cells by Activated Macrophages
Authors: Russell Stephen W , Pace Judith L , Varesio Luigi , Akporiaye Emmanuel , Blasi Elisabetta , Celado Antonio , Schreiber Robert D , Schultz Richard M , Stevenson Anita P , Stewart Carleton C , Stewart Sigrid J 
Published: January 2018

Abstract
Five different short term assays (&lt;48 h) used to measure macrophage-mediated, nonspecific cytotoxicity were compared under similar conditions in the same laboratory using the same reagents. The purpose was to determine the extent to which results were comparable. Three of the assays were dependent on the release of a radioisotope to measure cytotoxicity, one was dependent on cell counting, and the last was dependent on flow cytometric quantification of remaining viable tumor target cells after they had been exposed to macrophages. The variables examined were the following: a) three different populations of macrophages; b) four different kinds of target cells; c) two types of radioisotopes; and d) two different agents that trigger the expression of cytolytic activity by primed macrophages. Recombinant gamma interferon was used as the priming agent in all the experiments. There was unexpectedly good agreement between the results of the various assays. No differences were found among the different macrophage populations, the isotopes or the triggering agents. Perhaps the most important finding was that differences in target cell susceptibility to killing by activated macrophages, which were ap-
Polyanionic Agents Do Not Inhibit Phagosome-Lysosome Fusion in Cultured Macrophages
Authors: Goren Mayer B , Vatter Albert E , Fiscus Judith , Friedrich O A F 
Published: January 2018

Abstract
The survival of some intracellular pathogens within macrophages may be aided by an ability of the organism to antagonize, from within the entrapping phagosome, its fusion with lysosomes. On the other hand, certain polyanionic agents have been implicated in imposing a similar block to fusion from the lysosomal domain—because the transfer of various foreign markers from lysosomes to newly formed phagosomes is remarkably inhibited in these polyanion-containing cells. Based on an analysis of various observations and our own recent data, we propose that the polyanionics do not, in fact, prevent phagosome-lysosome fusion but, instead, physically entrap the usual markers in a gelatinous matrix within the lysosomes. This view accounts for many paradoxical consequences of polyanionic accumulation and for the curiously normal behavior of macrophages that are presumed to be suffering from such a crucial Intracellular dysfunction.
“This continuous search for truth can be a painful and punishing process. Sometimes it seems that all of education consists of first learning things and then learning that they are not true.”
Peripheral Blood Mononuclear Leukocytes Release a Mediator(s) That Induces Phagocytosis of C-Reactive Protein-Coated Cells by Polymorphonuclear Leukocytes
Authors: Kilpatrick J Michael , Gresham Hattie D , Griffin Frank M , Volanakis John E 
Published: January 2018

Abstract
We studied the phagocytosis by human polymorphonuclear leukocytes (PMN) of sheep erythrocytes (E) passively sensitized with pneumococcal C-polyseccharidc (E-PnC), E-PnC coated with C-resctive protein (E-PnC-CRP), and E coated with rabbit antisheep E IgG (E-lgG). PMN isolated from the blood of normal individuals failed to ingest either E-PnC or E-PnC-CRP; however, after incubation with supernatents from stimulated peripheral blood mononuclear leukocytes, glass adherent PMN ingested E-PnC-CRP with a mean phagocytic index of 47.8 ± 14.9 (means ± SD, n = 9) and E-PnC to a lesser extent with a phagocytic index of 9.6 ± 2.9 (mean ± SD, n = 4). We also observed a statistically significant increase in the ingestion of E-lgG by lymphokine-stimulated PMN with phagocytic indices of 85.2 ± 21.2 (mean ± SD, n = 12) for unstimulated PMN and 158 ± 37.1 (mean ± SO, n = 9) for stimulated PMN. The best conditions for stimulating release of this phagocytosis-promoting mediator included exposure to Phytohemagglutinin (PHA) in the presence of monocytes that had ingested lgG-coated sheep erythrocytes. The induction of phagocytosis of E-PnC-CRP was rapid, reaching a maximal level after stimulation of the adherent PMN with the conditioned media for 30 min. The factor(s) responsible for the induction of the ingestion of E-PnC-CRP was lees than 10,000 dations and was heat stable (56°C for 45 min). These data are similar to earlier results obtained with PMN activated by 12-0-tetradecanoyt-phoboi-13-acetale (PMA), an important contrast being that in the current studies PMN were activated by a soluble factor released from stimulated mononuclear cells under conditions simulating those in vivo.
Migration of Neutrophils From Lung to Tracheobronchial Lymph Node
Authors: Harmsen Allen G , Mason Margaret J , Muggenburg Bruce A , Gillett Nancy A , Jarpe Michael A , Bice David E 
Published: January 2018

Abstract
Translocation of particulate antigen deposited in the lung to tracheobronchial lymph nodes (TBLN) is important in the induction of pulmonary immune responses. We have previously shown that alveolar macrophages can contribute to particle translocation to TBLN, but whether neutrophils can ateo contribute to this process is not known. To determine if neutrophils can carry particles to the TBLN, dog neutrophils were elicited by instillation of red or green fluorescent microspheres into individual lung lobes. Autologous neutrophils that had phagocytized fluorescent microspheres were then Instilled Into an unexposed lobe of the same dog's lung. After 24 hr, the TBLN of instilled dogs had numerous neutrophils, 99% of which contained either red or green fluorescent microspheres but not both. Use of the two different colored microspheres as labels precluded the possibility that neutrophils had phagocytized the microspheres in the TBLN. In a second experiment, dogs were depleted of peripheral blood neutrophils by injections of hydroxyurea. Hydroxyurea treated and normal dogs were instilled with fluorescent microspheres and killed after 40 h. Hydroxyurea treatment reduced neutrophil accumulation in the lung by 79% and reduced particle translocation to the TBLN by 80%. Results of these experiments indicate that neutrophils are similar to pulmonary alveolar macrophages (PAM) In their ability to phagocytize particles in the lung and then migrate to the TBLN.
Receptor Binding and Activation of Polymorphonuclear Neutrophils by Tumor Necrosis Factor-Alpha
Authors: Shalaby M R , Palladino M A , Hirabayashi S E , Eessalu T E , Lewis G D , Shepard H M , Aggarwal B B 
Published: January 2018

Abstract
The interaction of highly purified recombinant human tumor necrosis factor-alpha (rTNF-α) with human polymorphonuclear neutrophils (PMNs) was investigated. Binding of 125l-rTNF-α to PMN reached maximum levels in 30 min at 37°C and in 2 h at 4°C. Scatchard analysis of competitive binding data indicated approximately 6000 receptor sites per cell and a Kd of 1.37 nM. Binding data at 37°C indicated a rapid internalization of rTNF-α. Following this receptor-mediated interaction, recombinant TNF-α was found to inhibit the migration of PMNs under agarose and to enhance PMN production of superoxide anion (O-2) in a dose-dependent manner. Furthermore, rTNF-α-activated PMNs caused a marked disruption of human umbilical-vein-derived endothelial cell monolayers and caused inhibition of their proliferative activities. These data substantiate the role of TNF-α as an activator of PMN functions and indicate that PMN/TNF-α/endothelial cell interactions may play a major role in inflammatory reactions.
Suppressive Effect of Interferon-β on Development of Tumoricidal Activity in Mouse Macrophages
Authors: Pace Judith L , MacKay Robert J , Hayes Mark P 
Published: January 2018

Abstract
The suppressive effect of IFN-alpha and IFN-beta on the induction of tumoricidal activity in mouse bone marrow-derived macrophages was investigated. Macrophages incubated for 24 hr with IFN-beta developed lower levels of cytolytic activity when stimulated with IFN-gamma and LPS, in comparison with macrophages pretreated with medium. The suppressive effect was dependent on the pretreatment dose of IFN-beta over a concentration range of 1 to 1,000 U/ml. Analysis of IFN-gamma dose response curves of IFN-beta treated macrophages showed that these cells were less sensitive to IFN-gamma. The suppressive effects were fully neutralized by an antiserum to IFN-alpha/beta. Prostaglandins were apparently not involved in this process since the addition of indomethacin to IFN-beta treated macrophages did not prevent the loss of responsiveness to activating stimuli. In contrast to the results obtained with IFN-alpha and IFN-beta, macrophages pretreated with IFN-gamma did not develop lower levels of cytolytic activity when again stimulated with IFN-gamma and LPS. These observations provide evidence for a potentially important negative regulatory role for IFN-alpha and IFN-beta in macrophage activation for tumor cell killing.
Monocytes from mobilized stem cells inhibit T cell function
Authors: Ino Kazuhiko , Singh Rakesh K , Talmadge James E 
Published: January 2018

Abstract
Granulocyte-macrophage colony-stimulating factor, mobilized peripheral blood stem cell (PSC) products, and peripheral blood leukocytes posttransplantation contain cells that cause allogeneic and autologous T cell apoptosis. Isolation and characterization of these cells demonstrated that they were low-density (Percoll fractionation) CD14+ monocytes. T cells in PSC products have a depressed phytohemagglutinin (PHA) mitogenic response; however, purified CD4+ or CD8+ T cells exhibit a statistically normal mitogenic function. Furthermore, no T cell inhibitory activity was observed in CD14+, CD4+, and CD8+ cell-depleted fractions enriched in CD4–CD8–TCRα/β+ T cells. Inhibition of T cell function by CD14+ monocytes required cell-cell contact, and the analyses of DNA fragmentation by Southern and TUNEL analysis demonstrates an activation-induced T cell apoptosis in the presence of CD14+ monocytes. Reverse-transcriptase polymerase chain reaction studies suggested that high levels of interleukin-10 or tumor necrosis factor gene transcripts in the PSC products may contribute to the inhibition of T cell function.
Phenotypic and functional differences between human dendritic cells derived in vitro from hematopoietic progenitors and from monocytes/macrophages
Authors: Triozzi Pierre L , Aldrich Wayne 
Published: January 2018

Abstract
We compared dendritic cells (DC) derived from CD34+ hematopoietic progenitor cells with tumor necrosis factor α and granulocyte-macrophage colony-stimulating factor (GM-CSF) to DC derived from monocytes/macrophages with interleukin-4 (IL-4) and GM-CSF. Monocyte/macrophage-derived DC demonstrated higher levels of CD1a, lower levels of CD14, greater stimulatory activity in mixed lymphocyte reactions, and greater capacity to present soluble protein antigen than CD34+ cell-derived DC. Lymphocytes stimulated with antigen-pulsed, monocyte/macrophage-derived DC produced more IL-10 than those stimulated with antigen-pulsed, CD34+-derived DC. Whereas CD1a+ DC could be derived from CD34+ cells in serum-free- and human-sera-containing cultures, the derivation of CD1a+ DC from monocytes/macrophages required the presence of fetal calf serum. The spectrum of cytokine mRNA expression, the presentation of peptide antigen, and the sensitivity to human immunodeficiency virus-1 infection of CD34+- and monocyte/ macrophage-derived DC were comparable. Although cells derived by both methods are potent antigen-presenting cells, there are differences between DC derived in vitro from hematopoietic progenitors and from monocytes/macrophages that may influence their in vivo activity.
Chemoattractant properties of PR-39, a neutrophil antibacterial peptide
Authors: Huang Hsuan-Jen , Ross Christopher R , Blecha Frank 
Published: January 2018

Abstract
The proline-arginine (PR) -rich antibacterial peptide, PR-39, kills bacteria by a non-pore-forming mechanism. Because this neutrophil peptide possesses several distinct functional properties and because other antimicrobial peptides are chemoattractants, we sought to determine whether PR-39 was a chemoattractant for porcine leukocytes. The peptide was synthesized by the solid-phase method using t-Boc chemistry and purified by reversed-phase high-performance liquid chromatography. Leukocyte migration was assessed with the use of a 48-well microchemotaxis chamber. PR-39 induced the directed migration of neutrophils. The peak chemotaxis response occurred at 0.5–2 μM, which was slightly lower than the minimal inhibitory and bactericidal concentrations for PR-39. However, the peptide was not a chemoattractant for mononuclear cells. Truncation of PR-39 suggested that the neutrophil chemoattractant domain may be contained within the first 26 amino acid residues. Intracellular Ca2+ fluxes in response to PR-39 were monitored by flow cytometry and showed a transient increase that peaked at approximately 40 s and approached basal values by 4 min. However, in a Ca2+-free environment, the PR-39-induced Ca2+ increase was abrogated. Furthermore, PR-39 did not induce neutrophil chemotaxis in the absence of extracellular Ca2+, and pertussis toxin inhibited both neutrophil chemotaxis and Ca2+ mobilization. Taken together, these data suggest that PR-39 is a Ca2+-dependent chemoattractant of neutrophils. The finding of a neutrophil antibacterial peptide that is also a neutrophil chemoattractant is intriguing and may indicate an important role for PR-39 in inflammation.
Cell-specific and inducible Nramp1 gene expression in mouse macrophages in vitro and in vivo
Authors: Govoni Gregory , Gauthier Susan , Billia Filio , Iscove Norman N , Gros Philippe 
Published: January 2018

Abstract
Mutations in the Nrampl gene abolish natural resistance to infections with many unrelated intracellular parasites in vivo. Global cDNA amplification was used to analyze Nrampl mRNA expression in bone marrow-derived cell colonies corresponding to either undifferentiated progenitors or to mature lymphoid, erythroid, and myeloid lineages. Nramp1 mRNA was detected in mature myeloid colonies expressing molecular markers for either the monocyte/macrophage or granulocytic lineages. Having established constitutive expression of Nramp1 in phagocytic cells, the parameters of inducible Nramp1 expression by cytokines and lipopolysaccharide (LPS) were studied in the mouse macrophage cell line RAW 264.7. LPS caused upregulation of Nramp1 expression in a time- and dose-dependent fashion. This induction required de novo protein synthesis and was abrogated by treatment with cycloheximide. Treatment with interferon-γ (IFN-γ) also caused a modest but reproducible twofold induction of Nramp1 mRNA expression. In addition, maximum Nramp1 mRNA induction in RAW 264.7 cells was observed after pretreatment with IFN-γ followed by LPS exposure. In vivo, Nramp1 mRNA expression could be upregulated in macrophage populations by intraperitoneal injection of either LPS or thioglycollate. Together these results indicate that Nramp1 is expressed in professional phagocytes of the myeloid lineage and can be further upregulated during macrophage activation in response to infectious, inflammatory, or cytokine stimuli. Finally, the patterns of constitutive and inducible expression of Nramp1 have been compared to those of the inducible nitric oxide synthase (iNOS) gene in the same cells.
Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8
Authors: Nishimura Akito , Akahoshi Tohru , Takahashi Michio , Takagishi Kenji , Itoman Moritoshi , Kondo Hirobumi , Takahashi Yuichi , Yokoi Kenji , Mukaida Naofumi , Matsushima Kouji 
Published: January 2018

Abstract
Accumulating evidence implicates interleukin-8 (IL-8) as an essential mediator in neutrophil-mediated acute inflammation. Neutrophils have also been shown to have a crucial role in the pathogenesis of acute gouty arthritis. Thus, we investigate the pathophysiological role of IL-8 in an experimental model of acute gout, monosodium urate (MSU) crystal-induced arthritis in rabbits. The injection of MSU crystals into knee joints caused a marked swelling of joints. Concomitantly, the infiltration of leukocytes, mostly neutrophils, was observed in synovial membrane and synovial fluids. The injection of MSU crystals also induced an elevation in synovial fluid IL-8 levels preceding neutrophil infiltration into synovial fluids, without an accompanying increase in plasma IL-8 levels. Immunoreactive IL-8 protein was detected in synovial lining cells at 12–24 h after the injection. IL-8 protein was also observed in infiltrated leukocytes in synovium as early as 3–24 h after the injection. Finally, the intraarticular injection of a neutralizing anti-IL-8 antibody significantly attenuated the crystal-induced joint swelling that occurred at 12 h, and neutrophil infiltration into arthritic joints at 12 and 24 h after the induction. These results provide evidence on the pathogenic roles of locally produced IL-8 in MSU crystal-induced gouty arthritis.
The role of shear forces in ischemia/reperfusion-induced neutrophil rolling and adhesion
Authors: Kubes Paul 
Published: January 2018

Abstract
Intravital microscopy was used to examine the role of reduced shear forces on neutrophilendothelium interactions in single 25–40 μm diameter vessels in the feline postischemic mesenteric microvasculature. Neutrophil rolling, neutrophil adhesion, and microvascular permeability alterations were determined in vessels exposed to ischemia/reperfusion in untreated animals and in cats that received feline plasma directly into the superior mesenteric artery to increase intestinal blood flow and venular shear rates. Ischemia, followed by reperfusion, caused a profound increase in venular shear forces during the initial hyperemic response, which then decreased to below control values by 10 min of reperfusion and to less than 50% of control by 60 min of reperfusion. Associated with the decrease in blood flow was a profound increase in neutrophil rolling and neutrophil adhesion and an increase in microvascular permeability. Also, leukocyte rolling velocity decreased dramatically to 10–20% of control values during the first 10 min of reperfusion. Infusion of autologous plasma into the intestinal vasculature to maintain the shear forces at control levels during reperfusion did not affect the flux of rolling neutrophils. The rolling velocity of the neutrophils was not increased despite dramatically improved shear rates. Improved shear rates did reduce the number of adherent cells, resulting in less vascular dysfunction. The reduction in shear forces through inflamed microvessels does not contribute to the increased leukocyte rolling flux but is an essentential, permissive component for neutrophil adhesion and subsequent vascular dysfunction in postischemic microvasculature.