bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon α-induced changes in FcγR-specific mRNA expression and isotype-specific, FcγR-mediated phagocytosis in C3H/OuJ (Lpsn) and C3H/HeJ (Lpsd) macrophages
Authors: Fultz Marion J , Vogel Stefanie N 
Published: January 2018

Abstract
Peritoneal exudate macrophages from C3H/OuJ (Lpsn) and C3H/HeJ (Lpsd) mice were treated with interferon α (IFN-α), and isotype-specific phagocytosis and gene expression were measured. IFN-α selectively augments phagocytosis of IgG2a, with a highly significant induction of FcγRI mRNA expression, while parallel FcγRIIIα measurements show a relatively small increase.
Charcot-Leyden crystal protein in the degranulation and recovery of activated basophils
Authors: Golightly Linnie M , Thomas Larry L , Dvorak Ann M , Ackerman Steven J 
Published: January 2018

Abstract
The Charcot-Leyden crystal (CLC) protein, a prominent cell constituent unique to eosinophils and basophils, possesses lysophospholipase activity. This activity and the extracellular deposition and formation of CLC in tissues and body fluids in association with eosinophils suggest an extracellular function for this protein in inflammation. During degranulation, basophils release granule-derived mediators of inflammation. We postulated that CLC protein, localized in part to the basophil granule, might be released along with other mediators during this process. The extracellular release of CLC protein was studied during the degranulation of basophils stimulated by anti-immunoglobulin E (anti-IgE), N-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate, eosinophil major basic protein (MBP), and calcium ionophore A23187. Histamine release was used as a marker of basophil degranulation; its release was measured utilizing the fluorometric technique. CLC protein was not released into the supernatant during this process as determined by radioimmunoassay. CLC protein in the extracellular space, either as intact crystals or aggregates, was undetectable by indirect immunofluorescent staining of basophils activated with either anti-IgE or fMLP. However, upon activation, the immunofluorescent cytoplasmic and nuclear staining pattern for CLC protein was significantly altered. Decreased cytoplasmic staining and persistent or increased nuclear staining for CLC protein were observed after activation, with recovery of the preactivation, unstimulated cellular staining pattern at 30 and 45 min after stimulation with fMLP and anti-IgE, respectively. These findings suggest that CLC protein functions intracellularly in basophils during the process of activation, degranulation, and recovery. The potential nuclear function(s) of this lysophospholipase in the basophil requires further investigation.
C5a and formyl peptide receptor regulation on human monocytes
Authors: van Epps Dennis E , Simpson Stacy J , Chenoweth Dennis E 
Published: January 2018

Abstract
Regulation of C5a and formyl-methionine-leucine-phenylalanine-lysine (fMLPL) receptors on human monocytes has been studied using fluorescein-conjugated derivatives and flow cytometry. Monocytes have receptors for each of these ligands, as evidenced by their ability to bind specifically biologically active fluorescein derivatives of these ligands. Quenching experiments showed that bound fluoresceinated C5a and fMLPL are rapidly internalized at 37°C. Once internalized, monocytes are able to reexpress these receptors, returning to control levels within approximately 90 min. This contrasts with rate differences seen in polymorphonuclear neutrophils (PMNs), where fMLPL receptors return more rapidly (~ 30 min) than do C5a receptors (~ 100 min). Monensin inhibited the reexpression of C5a but not fMLPL receptors, suggesting that a receptor recycling process is necessary to replenish C5a receptors on the monocyte surface. Similar although less efficient inhibition of C5a receptor reexpression was observed with NH4Cl treatment. Reexpression of both G5a and fMLPL receptors was independent of extracellular Ca2+. Treatment with various agents known to stimulate monocytes and PMNs increased the expression of fMLPL receptors in both cell types but either had no effect on or reduced the level of C5a receptor expression. This would indicate that monocytes, like PMNs, have intracellular pools of preformed fMLPL receptors, available for reexpression. These studies show that, like PMNs, monocytes modulate C5a and fMLPL receptors through different mechanisms. Furthermore, monocytes are capable of reexpressing these receptors following exposure to ligand, a theoretical requirement for chemotaxis.
Effect of circulating neutrophil depletion on lung injury induced by inhaled silica particles
Authors: Gavett Stephen H , Carakostas Michael C , Belcher Leigh A , Warheit David B 
Published: January 2018

Abstract
Polymorphonuclear leukocytes (PMNs) recruited into the alveolar region during inflammation may injure the lung parenchyma by releasing cytotoxic oxygen radicals and proteases. Because brief exposures to crystalline silica elicit recruitment of PMNs into the alveolar region, which is strongly correlated with parameters of cytotoxicity, increased alveolar epithelial permeability, and lysosomal enzyme release, we sought to evaluate the potential role of PMNs in silica-induced lung injury. Rats were depleted of PMNs by administration of an anti-rat PMN antiserum prior to exposure to silica. Pulmonary inflammatory responses to silica in this group were compared to responses in normal silica-exposed rats as well as sham-exposed normal or PMN-depleted rats. Bronchoalveolar lavage fluids from normal, silica-exposed rats contained 9.7 × 106 PMNs immediately after exposure for 3 days, compared to 0.01 × 106 PMNs for both normal or PMN-depleted, sham-exposed rats. Bronchoalveolar lavage fluids from successfully PMN-depleted, exposed rats contained significantly fewer (0.7 × 106) PMNs compared to normal silica-exposed rats. In both groups of silica-exposed rats, a variety of biochemical indicators of lung injury were increased significantly compared to measurements from both sham-exposed groups, but there were no differences between PMN-depleted and normal silica-exposed groups. The results suggest that recruitment of PMNs into the alveolar region is not a necessary prerequisite for the observed increases in biochemical indicators of silica-induced acute lung injury.
Chondroitin sulfate proteoglycan and heparan sulfate proteoglycan production by cultured pigeon peritoneal macrophages
Authors: Owens Rick T , Wagner William D 
Published: January 2018

Abstract
Proteoglycan production was examined in cultures of thioglycollate-elicited peritoneal macrophages obtained from White Carneau and Show Racer pigeons. Following a 24-h incubation in the presence of [35S]sulfate and [3H]serine, total production and distribution of 35S-labeled proteoglycan into media (60–65%), pericellular (21–27%), and intracellular (13–14%) compartments was similar in White Carneau and Show Racer macrophage cultures. Media proteoglycans consisted of high-molecular-weight chondroitin sulfate proteoglycan, low-molecular-weight chondroitin sulfate proteoglycan, and heparan sulfate proteoglycan. High-molecular-weight chondroitin sulfate proteoglycan was predominantly 6-sulfated (80%) and contained a core protein larger than 200 kd, whereas low-molecular-weight chondroitin sulfate proteoglycan was 4-sulfated and contained a 28-kd core protein. Pericellular proteoglycan was similar in size to low-molecular-weight proteoglycan and consisted of a predominantly 6-sulfated (75%) chondroitin sulfate proteoglycan and heparan sulfate proteoglycan. Intracellular 35S-labeled chondroitin sulfate and heparan sulfate were smaller than media and pericellular proteoglycans, suggestive of intracellular degradative processing.
Listericidal and nonlistericidal mouse macrophages differ in complement receptor type 3-mediated phagocytosis of L. monocytogenes and in preventing escape of the bacteria into the cytoplasm
Authors: Drevets Douglas A , Canono Beth P , Campbell Priscilla A 
Published: January 2018

Abstract
Listeria monocytogenes is a facultative intracellular bacterium that escapes phagocytic vesicles and replicates in the cytoplasm, where it becomes coated with F-actin. Macrophages, important anti-Listeria effector cells, are heterogeneous in their ability to kill Listeria. Complement receptor type 3 (CR3) mediates most phagocytosis of Listeria by listericidal macrophages. Experiments described here tested whether nonlistericidal macrophages also phagocytosed Listeria through CR3 and whether the ability of Listeria to escape into the cytoplasm correlated with lack of listericidal activity. We show here that CR3 mediated an average of 66% of the phagocytosis of serum-opsonized Listeria by listericidal peptone-elicited macrophages but only 35% by nonlistericidal thioglycolate-elicited macrophages. In thioglycolate-elicited macrophages, most Listeria were cytoplasmic and actin coated, whereas in peptone-elicited macrophages most were retained in the phagosome. These results indicate that listericidal and nonlistericidal macrophages phagocytose Listeria through different receptors and that nonlistericidal macrophages allow Listeria to escape into the cytoplasm.
Effects of phenobarbital on leukocyte activation: membrane potential, actin polymerization, chemotaxis, respiratory burst, cytokine production, and lymphocyte proliferation
Authors: Yang Kuender D , Liou Wen-Yu , Lee Chung-Shinn , Chu Meng-Ling , Shaio Men-Fang 
Published: January 2018

Abstract
Leukocyte activation is known to involve cell membrane potential changes. Phenobarbital, an anesthetic and anticonvulsant that can inhibit neuronal membrane depolarization, may also affect leukocyte activation. Measuring membrane potential, actin polymerization, chemotaxis, superoxide production, lymphocyte proliferation, intracellular calcium concentration, and cytokine production, we found that phenobarbital at a concentration of 15–30 μg/ml, which is considered a therapeutic serum level for controlling seizures, did not affect polymorphonuclear neutrophil (PMN) activation. At levels higher than 100 μg/ml, phenobarbital significantly suppressed formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis. Concentrations greater than 300 μg/ml also inhibited phorbol myristate acetate–stimulated membrane potential change. In contrast, 30 fig/ml phenobarbital significantly inhibited lymphocyte proliferation stimulated by phytohemagglutinin (PHA) and pokeweed mitogen. This concentration of phenobarbital also suppressed the increase of intracellular free calcium induced by PHA. However, only a higher concentration of phenobarbital (300 μg/ml) was able to inhibit PHA-induced interleukin-2 (IL-2) production and suppress the proliferation of PHA-induced IL-2 receptor–bearing lymphocytes. These results suggest that concentrations of phenobarbital associated with anticonvulsive levels do not affect PMN activation but suppress lymphocyte activation, possibly by affecting intracellular signal transduction.
Interferon-γ and Interleukin-4 down-regulate soluble CD14 release in human monocytes and macrophages
Authors: Landmann Regine , Fisscher Ada E , Obrecht Jean-Paul 
Published: January 2018

Abstract
CD14 is a 53-kd glycoprotein that is mainly expressed in myeloid cells and exists in two forms. The membrane-bound form represents the receptor for complexes of lipopolysaccharide (LPS) with LPS binding protein. The function and regulation of the soluble form are unknown. In the present study we investigated the release of soluble CD14 (sCD14) in cultures of human mononuclear leukocytes, elutriated monocytes, and monocyte-derived macrophages. The release of sCD14 into the medium of the cells cultured for 15 and 45 h was investigated in the absence or presence of selected cytokines. sCD14 release occurred constitutively and correlated with cell number. In monocytes differentiating into macrophages, cumulative release of sCD14 was linear from day 1 to day 7. Spontaneous sCD14 release after 15 h of culture (2 × 106 cells/ml) was higher in the supernatant from monocytes (314 ± 58 ng/ml) than that from mononuclear leukocytes (68 ± 10 ng/ml) and similar to that from macrophages (469 ± 79 ng/ml). Cycloheximide and actinomycin D inhibited sCD14 release. Recombinant interferon-γ (rIFN-γ) and recombinant interleukin-4 (rIL-4) directly decreased sCD14 release in mononuclear leukocyte, monocyte, and macrophage cultures. rIL-2 and rIFN-α reduced sCD14 release into the supernatants of mononuclear leukocytes only. Use of anti-IFN-γ antibodies indicated that the down-regulation of sCD14 release by rIL-2 and rIFN-α was partially due to induction of endogenous IFN-γ. The down-regulation of sCD14 release by all four cytokines was both time and dose dependent. rIFN-γ and rIL-4 added simultaneously had a synergistic effect on sCD14 down-regulation. In conclusion, sCD14 release may have an immunomodulatory role in circulating monocytes, is apparently not related to the process of macrophage differentiation, and is selectively down-regulated during an immune response when levels of IFN-γ and IL-4 are high.
Mepacrine inhibits fMLP-induced activation of human neutrophil granulocytes, leukotriene B4 formation, and fMLP binding
Authors: Földes-Filep Éva , Filep János G 
Published: January 2018

Abstract
Pulmonary sequestration and activation of polymorphonuclear leukocytes (PMNLs) are characteristic of many forms of acute lung injury. The present experiments were designed to study the effects of mepacrine on human neutrophils challenged with N-formylmethionyl- leucyl-phenylalanine (fMLP). Mepacrine inhibited fMLP-induced superoxide production and degranulation in a dose-dependent manner with Kd values of 2.3 ± 0.5 × 10−7 M and 5.7 ± 1.3 × 10−6 M, respectively. Stimulation of PMNLs by 10−6 M fMLP provoked the formation of barely detectable amounts of leukotriene B4 (LTB4) (&lt; 5 pg/107 cells). Pretreatment of the cells with cytochalasin B augmented generation of LTB4 in response to fMLP (339 ± 79 pg/107 cells). LTB4 formation was also inhibited by mepacrine (50% inhibitory concentration 1.0 ± 0.5 × 10−6 M). Furthermore, mepacrine inhibited the specific binding of [3H]fMLP to neutrophils with a Ki value of 1.4 ± 0.4 ˟ 10”5 M. Mepacrine decreased the receptor binding affinity without altering the number of receptors. These findings demonstrate that the inhibitory effect of mepacrine is response dependent and suggest that this action of mepacrine could, in part, be attributed to a decrease in fMLP receptor affinity.
Macrophage priming by interferon gamma: a selective process with potentially harmful effects
Authors: Williams John G , Jurkovich Gregory J , Hahnel Greg B , Maier Ronald V 
Published: January 2018

Abstract
The tissue-fixed macrophage is a key cellular element in the initiation and regulation of inflammation. Understanding the regulation of macrophage activation may provide valuable clues to the mechanisms involved in both beneficial and deleterious effects of inflammation. The lymphokine interferon-γ (IFN-γ) is capable of producing paradoxical immunoinflammatory effects. In the immunocompromised host it up-regulates a variety of immune functions and improves survival, but it is also capable of producing harmful effects by sensitizing immunocompetent animals to subclinical doses of endotoxin. These paradoxical effects suggest that the state of activation or priming of the host immune system is a key determinant of its response to endotoxemia. Because tumor necrosis factor (TNF) and procoagulant activity (PCA) elaboration by the tissue-fixed macrophage play a central role in the host response to endotoxin, we asked whether the paradoxical effects of IFN-γ may be caused by priming of the macrophage for TNF and/or PCA production. In vitro, IFN-γ produces a marked augmentation in TNF but does not alter PCA elaboration in response to endotoxin, demonstrating the selectivity of IFN-γ priming of the macrophage. In vivo, IFN-γ pre- treatment followed by an established subclinical endotoxin exposure enhances toxicity while simultaneously increasing peak serum TNF levels. Exogenous priming by IFN-γ alters the activation state of the macrophage and modifies the host response to endotoxin. Because this response is also dependent on the host's underlying immune state, IFN-γ treatment in the immunocompetent host has the potential to produce deleterious effects by eliciting an exaggerated TNF response during endotoxemia.
Killing of Legionella pneumophila by nitric oxide in γ-interferon-activated macrophages
Authors: Summersgill James T , Powell Lori A , Buster Brad L , Miller Richard D , Ramirez Julio A 
Published: January 2018

Abstract
The role of nitric oxide (NO) radicals in killing the intracellular bacterial pathogen Legionella pneumophila (Lp) was examined in infected macrophages. Murine (RAW 264.7) and human (HL-60) cell monolayers were treated with 100 U/mlγ-interferon (IFN) and cocultured with Lp in the presence and absence of NGMMA, a specific inhibitor of NO production. Viable Lp in IFN-treated RAW 264.7 cells decreased from 3.8 to 0.7 ± 0.12 log CFU/ml after 24 h incubation, whereas in IFN + NGMMA-treated RAW 264.7 cells, viable Lp persisted at 2.2 ± 0.2 log CFU/ml after 24 h. This increased survival corresponded with an inhibition of NO production (5.65 ± 2.99 μM with NGMMA vs. 58.6 ± 5.36 μM without NGMMA). Viable Lp were susceptible to killing, in a dose-dependent fashion, by 0, 2.5, and 5.0 mM sodium nitroprusside, a source of NO radicals. IFN-treated RAW 264.7 cells also had significantly decreased levels of intracellular iron (below assay limit) when compared to IFN + NGMMA-treated cells (72.0 ± 0.78 % of control). Normally permissive HL-60 cells treated with IFN were bacteriostatic rather than bactericidal, and NO production was not detected above background. Thus, NO radicals play a critical role in the bactericidal activity against Lp by IFN-treated RAW 264.7 cells, but the absence of NO production limits IFN-treated HL-60 cells to bac- teriostasis.
Differentiation of dendritic cell populations in macrophage colony-stimulating factor-deficient mice homozygous for the osteopetrosis (op) mutation
Authors: Takahashi Kiyoshi , Naito Makoto , Shultz Leonard D , Hayashi Shin-ichi , Nishikawa Shin-ichi 
Published: January 2018

Abstract
In op/op mice, immunohistochemical and electron microscopic techniques were used to examine the effects of the OP mutation on dendritic cell populations in lymphoid tissues and skin. In the thymic medulla, T cell zone of lymph nodes, and splenic white pulp of op/op mice, numbers of NLDC-145-positive dendritic cells were not decreased. Compared to the normal litter- mates, numbers of BM8-positive macrophages were reduced in various tissues of the mutant mice, including the lymphoid tissues. These dendritic cells of op/op mice expressed la antigens but not F4/80 and BM8 antigens. Ultrastructurally, the dendritic cells developed a tubulo- vesicular system typical of interdigitating cells, but they were abnormal in that interdigitation of their cytoplasmic processes was not prominent. In the epidermis of the op/op mice, dendritic cells expressed NLDC-145, F4/80, la antigens, and adenosine diphosphatase or adenosine triphosphatase activity, and numbers of NLDC-145-, la-, or ADPase-positive dendritic cells were reduced slightly, but these reductions were not significant statistically. Bir- beck granules were detected in most of them electron microscopically. These results indicate that nonlymphoid dendritic cells develop in the lymphoid tissues and skin of op/op mouse, suggesting that they are differentiated from granulocyte-macrophage colony-forming cells or earlier hematopoietic cell precursors. J. Leukoc. Biol. 53: 19–28; 1993.
Platelet-activating factor–induced calcium mobilization and oxidative metabolism in hepatic macrophages and endothelial cells
Authors: Gardner Carol R , Laskin Jeffrey D , Laskin Debra L 
Published: January 2018

Abstract
Fluorescence image analysis of the calcium sensitive dye Indo-1 was used to characterize platelet-activating factor (PAF)-induced calcium mobilization in hepatic macrophages and endothelial cells. PAF, but not lyso-PAF, an inactive analog, induced a rapid and transient increase in intracellular levels of calcium that appeared to depend on the presence of extracellular calcium. In both macrophages and endothelial cells, these effects were dose dependent, reaching maximal levels with 10 nM PAF. However, the kinetics of the calcium response to PAF in macrophages and endothelial cells was distinct. The endothelial cells responded more rapidly to PAF than the macrophages (within 1 min vs. 2-3 min, respectively) and displayed longer recovery periods (4 min vs. &gt;10 min, respectively). In contrast, the magnitude of the response to PAF was greater in the macrophages. In both cell types, triazolam and alprazolam, two PAF antagonists, and the calcium channel blocker verapamil inhibited PAF-induced calcium mobilization. PAF also stimulated superoxide anion production alone and in combination with the macrophage activator 12-0- tetradecanoyl-phorbol-13-acetate (TPA) in both cell types. Macrophages produced more of this reactive oxygen intermediate in response to PAF and TPA than endothelial cells. Interestingly, in the absence of extracellular calcium or when verapamil was added to the cultures, superoxide anion production by the macrophages, but not the endothelial cells, was significantly reduced. These results demonstrate that, although hepatic macrophages and endothelial cells mobilize calcium in response to PAF, the characteristics of the response in each cell type are different. These differences may underlie, at least in part, distinct functional responses of the cells to PAF. J. Leukoc. Biol. 53: 190–196; 1993.
Characterization of neutrophil activation by repeated injection of endotoxin in rabbits. Role of neutrophils in the generalized Shwartzman reaction
Authors: Toh Hiroto , Miyata Tadanori , Torisu Motomichi 
Published: January 2018

Abstract
The relationship between activated neutrophils and end-organ injury in endotoxemia was studied. The function of peripheral blood neutrophils (PMNs) in rabbits with the generalized Shwartzman reaction (GSR) was compared to that of PMNs rabbits receiving a single injection of endotoxin. The following results were obtained: (1) PMNs from rabbits with the GSR demonstrated enhanced adherence to endothelial cells and increased mitochondrial ATP production; (2) the GSR did not enhance chemotaxis and oxygen radical production of PMNs; (3) a single injection of endotoxin did not cause necrosis of visceral organs; (4) in vitro detachment of endothelial cells by PMNs was increased in rabbits with the GSR; (5) in vivo administration of monoclonal antibody (mAb) against CD1lb/CD 18 (Mac-1) suppressed the increase in PMN adherence; and (6) hemorrhagic necrosis did not occur when mAb to Mac-1 was injected. Thus, enhanced adherence of PMNs to endothelial cells appears to play a key role in endotoxin-induced end-organ injuries in this animal model. J. Leukoc. Biol. 53: 256–263; 1993.