bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional evidence for microglial expression of C1qRP, the C1q receptor that enhances phagocytosis
Authors: Webster Scott D , Park Minha , Fonseca Maria I , Tenner Andrea J 
Published: January 2018

Abstract
Microglial activation has been associated with several degenerative diseases of the central nervous system (CNS). One consequence of activation is the induction of a more efficient phagocytic response, and it is therefore important to determine what factors regulate microglial phagocytosis and whether this capacity influences the progression of neurodegenerative changes. Previous studies have demonstrated that complement component C1q enhances Fc receptor- and CR1-mediated phagocytosis in cells of the myeloid lineage via a cell surface receptor, C1qRP. Because C1q has been found in the area of lesions in several degenerative CNS diseases, the current investigations were carried out to characterize the effects of C1q on microglial phagocytosis. Neonatal rat microglia were shown to express C1qRP as assessed by flow cytometry and immuno-cytochemistry. Interaction of these cells with substrate-bound C1q was shown to enhance both FcR-and CR1-mediated phagocytosis two- to fourfold. In addition, introduction of an antibody raised against the carboxy-terminal, cytoplasmic domain of C1qRP into microglia by electroporation markedly diminished the ability of C1q to enhance uptake of IgG-coated targets, whereas nonspecific IgG had no such effect. These results suggest that C1q in areas of active degeneration may promote the phagocytic capacity of microglia via interaction with microglial C1qRP. J. Leukoc. Biol. 67: 109–116; 2000.
Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli
Authors: Buechler Christa , Ritter Mirko , Orsó Evelyn , Langmann Thomas , Klucken Jochen , Schmitz Gerd 
Published: January 2018

Abstract
CD163, also referred to as M130, a member of the scavenger receptor cysteine-rich family (SRCR) is exclusively expressed on cells of the monocyte lineage. In freshly isolated monocytes the CD14bight CD16+ monocyte subset revealed the highest expression of CD163 among all monocyte subsets. CD163 mRNA and protein expression is up-regulated during macrophage colony-stimulating factor (M-CSF)-dependent phagocytic differentiation of human blood monocytes. In contrast, monocytic cells treated with GM-CSF and interleukin-4 (IL-4) for dendritic differentiation down-regulate this antigen. CD163 expression is also suppressed by proinflammatory mediators like lipopolysaccharide (LPS), interferon-γ (IFN-γ), and tumor necrosis factor α, whereas IL-6 and the antiinflammatory cytokine interleukin-10 (IL-10) strongly up-regulate CD163 mRNA in monocytes and macrophages. The effects of the immunosuppressants dexamethasone, cyclosporin A (CA), and cortisol differ in their capacity to influence CD163 mRNA levels. Our results demonstrate that CD163 expression in monocytes/macrophages is regulated by proinflammatory and antiinflammatory mediators. This expression pattern implies a functional role of CD163 in the antiinflammatory response of monocytes. J. Leukoc. Biol. 67: 97–103; 2000.
In vivo administration of GM-CSF promotes the clearance of apoptotic cells: effects on monocytes and polymorphonuclear leukocytes
Authors: Galati Giacomo , Rovere Patrizia , Citterio Giovanni , Bondanza Attilio , Scaglietti Ugo , Bucci Eraldo , Heltai Silvia , Fascio Umberto , Rugarli Claudio , Manfredi Angelo A 
Published: January 2018

Abstract
The clearance of apoptotic cells is crucial to avoid chronic inflammation and autoimmunity. Little is known about the factors that regulate it in vivo. We show that granulocyte-macrophage colony-stimulating factor (GM-CSF) administration to carcinoma patients confers to their leukocytes a significantly higher ability to phagocytose apoptotic cells than before (P &lt; 0.005). GM-CSF increased the concentration of monocytes and polymorphonuclear leukocytes in the peripheral blood and activated circulating polymorphonuclear leukocytes. Both effects abated early after treatment, whereas phagocytosis of apoptotic cells was still significantly higher after 18 days compared with basal values (P &lt; 0.005 and P &lt; 0.025 for monocytes and polymorphonuclear leukocytes, respectively). On in vitro phagocytosis of apoptotic cells monocytes, but not polymorphonuclear leukocytes, up-regulated MHC class II membrane expression. These findings are consistent with the possibility that GM-CSF endows both scavenger and antigen-presenting leukocytes with the ability to internalize apoptotic tumor cells. J. Leukoc. Biol. 67: 174–182; 2000.
Regulation of ICAM-1/CD54 expression on human endothelial cells by hydrogen peroxide involves inducible NO synthase
Authors: Zadeh Majid Sadeghi , Kolb Jean-Pierre , Geromin Daniela , D'Anna Rossella , Boulmerka Amira , Marconi Anthony , Dugas Bernard , Marsac Cécile , D'Alessio Patrizia 
Published: January 2018

Abstract
Expression of the inducible isoform of nitric oxide synthase (iNOS) is stimulated by cytokines in human epithelial cells. This work indicates that incubation of human umbilical cord endothelial cells with combinations of interleukin-1β, tumor necrosis factor α, and interferon-γ stimulated the synthesis of iNOS mRNA, as detected by reverse transcriptase-polymerase chain reaction. It is important to note that 50, 100, and 200 μM hydrogen peroxide was able to stimulate iNOS directly. Furthermore, 100 μM H2O2 enhanced synthesis of the oxidation products, nitrite (NO) and nitrate (NO) at 12 and 36 h. iNOS protein, detected by Western blot analysis, as well as L-citrulline levels, were also increased. When endothelial cell monolayers were incubated for 1 h with 100 μM H2O2 and subsequently with cytokines, iNOS mRNA was further augmented. Under the same conditions, we regularly observed an inhibition (25%) of intercellular adhesion molecule-1 (ICAM-1/CD54) expression. The latter was reversed when the NOS inhibitor NG-monomethyl-L-arginine was added, as shown by flow cytometry. These data suggest a specific effect of endogenous hydroperoxides on the biosynthesis and processing of the human endothelial iNOS isoform. We propose that H2O2 induces a temporary NO-dependent modulation of adhesion molecule expression to limit the tissue destruction that accompanies the vascular recruitment of leukocytes. J. Leukoc. Biol. 67: 327–334; 2000.
Effects of heme proteins on nitric oxide levels and cell viability in isolated PMNs: a mechanism of toxicity
Authors: Cassidy Richard A , Burleson David G , Delgado Angel V , Kohler Dennis J , Salin Marvin L , Pruitt Basil A 
Published: January 2018

Abstract
Isolated human PMNs served as a model to determine oxyhemoglobin (oxyHb) binding and the effects of oxymyoglobin (oxyMb) or oxyHb on production of both nitric oxide (NO·) and superoxide (O2) and the resulting cytotoxicity. Physiologically relevant concentrations of NO and H2O2 oxidized, to a similar extent, 2,7-dichlorodihydro-fluorescein (DCFH) loaded into polymorphonuclear neutrophils (PMNs). Activation of PMNs with phorbol 12-myristate 13-acetate (PMA) markedly increased the internalization of extracellular oxyHb (10–250 μg/mL). OxyMb (10–300 μg/mL) or oxyHb (30–300 μg/mL) enhanced DCFH oxidation by a concentration-dependent mechanism in unstimulated, lipopolysaccharide (LPS) and tumor necrosis factor a (TNF-α)-, and PMA-stimulated PMNs. This increased DCFH oxidation was eliminated by NO synthase inhibitors, glutathione and ascorbate, and was reduced by albumin. Nitrite accumulation in PMN filtrates mirrored NO-induced DCF fluorescence. OxyMb-induced increases in NO levels paralleled alterations in DNA and cell membrane damage and ATP levels in PMNs and co-cultured lymphocytes, and were attenuated by NO synthase inhibitors. OxyMb eliminated extracellular O2 at protein concentrations 100- to 1000-fold above those of superoxide dismutase. These results suggest that heme proteins bind and internalize into PMNs and increase NO-induced damage in neighboring cells by inhibiting O2 -scavenging of NO We propose a mechanism whereby heme protein-induced NO levels may contribute to immunosuppression and increased infection rates associated with transfusions and cellular damage during inflammation. J. Leukoc. Biol. 67: 357–368.
Immune response to infection with Salmonella typhimurium in mice
Authors: Mittrücker Hans-Willi , Kaufmann Stefan H E 
Published: January 2018

Abstract
Infection of mice with Salmonella typhimurium results in systemic infection and a disease similar to that seen in humans after infection with S. typhi. The innate immune system can restrict replication of S. typhimurium to a certain degree, but for effective control and eradication of bacteria, acquired immunity is essential. Salmonella infection induces the generation of specific CD4+ and CD8+ T cells, and both T cell populations are important for protection during primary and secondary responses, although the mechanisms underlying T cell-mediated protection are not yet completely understood. Infection with S. typhimurium also results in a strong antibody response to Salmonella antigens and, in contrast to most other intracellular bacteria, this antibody response participates in protection. In summary, the response to S. typhimurium involves both T and B cell-mediated immunity, and mechanisms mediated by both lymphocyte populations are important for control of primary infection and protection against secondary infection. J. Leukoc. Biol. 67: 457–463; 2000.
A flow cytometric immune function assay for human peripheral blood dendritic cells
Authors: Willmann Kerstin , Dunne John F 
Published: January 2018

Abstract
CD11c+ and CD11c− (CD123+) dendritic cells (DCs) have been described in blood. Both cell types express high levels of HLA-DR and lack the lineage markers CD3, CD14, CD19, CD20, CD16, and CD56. These immunophenotypic properties were used along with analysis of activation-related surface antigens and intracellular staining of cytokines to characterize functional responses of these DC subsets to stimuli in whole human blood (WB). Samples from healthy donors were activated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate plus ionomycin (PMA+I). The only distinct response in CD11c−DCs was the expression of CD25 upon PMA+I activation. CD11c+ cells responded to LPS stimulation by producing high levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), and lower levels of IL-6, IL-1Ra, and IL-8 and an increased expression of accessory molecules (CD25, CD40, CD80, CD86, HLA-DR, and HLA-DQ). PMA+I activation of CD11c+ cells resulted in high levels of IL-1p and lower levels of IL-8, IL-1Ra, and TNF-ct and up-regulation of CD80, CD86, HLA-DR, and HLA-DQ. Our data support prior observations of functional differences between peripheral blood DC subsets and demonstrate the power of multiparameter flow cytometry to characterize the pleiotropic responses of these cells to various stimuli. J. Leukoc. Biol. 67: 536–544; 2000.
Lack of IL-10 synthesis by murine alveolar macrophages upon lipopolysaccharide exposure. Comparison with peritoneal macrophages
Authors: Salez Laurent , Singer Monique , Balloy Viviane , Créminon Christophe , Chignard Michel 
Published: January 2018

Abstract
The central role of alveolar macrophages in the establishment of lipopolysaccharide (LPS)-induced lung inflammation is well demonstrated. They produce and release numerous proinflammatory molecules, among which is tumor necrosis factor α (TNF-α), a cytokine responsible in part for the neutrophilic alveolitis. Interleu-kin-10 (IL-10) produced by LPS-activated mononuclear phagocytes is a major anti-inflammatory cytokine that down-regulates TNF-α synthesis. We studied the ability of murine alveolar macrophages to produce IL-10 in vivo and in vitro, in response to LPS. Unexpectedly, the IL-10 protein was not detected in the whole lung and airspaces after LPS intranasal instillation. In addition, no IL-10 protein was found in supernatants of isolated and LPS-stimulated alveolar macrophages. The lack of IL-10 synthesis was confirmed by the absence of specific RNA transcripts. By contrast and as expected, autologous peritoneal macrophages produced IL-10 upon LPS challenge. Drugs that usually modify the TNF-α/IL-10 balance in favor of IL-10 were used without success. Thus, maneuvers allowing an increase in intracellular cAMP concentrations did not reverse this unexpected phenotype. Moreover, direct activation of protein kinase C with PMA was unable to trigger IL-10 formation by alveolar, by contrast to peritoneal, macrophages. The current findings describe a specific phenotype for murine alveolar macrophages during LPS-induced inflammation. J. Leukoc. Biol. 67: 545–552; 2000.
Inflammatory neutrophils retain susceptibility to apoptosis mediated via the Fas death receptor
Authors: Renshaw Stephen A , Timmons Samantha J , Eaton Vanessa , Usher Lynne R , Akil Mohammed , Bingle Colin D , Whyte Moira K B 
Published: January 2018

Abstract
Apoptosis and clearance of neutrophils is essential for successful resolution of inflammation. Altered signaling via the Fas receptor could explain the observed prolongation of neutrophil lifespan and associated tissue injury at inflammatory sites. We therefore compared inflammatory neutrophils extracted from joints of rheumatoid arthritis patients, with peripheral blood neutrophils. Inflammatory neutrophils underwent constitutive apoptosis in culture more rapidly than peripheral blood neutrophils; this was not explained by changes in surface expression of Fas or by induction of Fas ligand. Inflammatory neutrophils remained sensitive to Fas-induced death, at levels comparable to those seen in peripheral blood neutrophils. Similarly, granulocyte-macrophage colony-stimulating factor reduced apoptosis but did not abolish signaling via Fas. These data provide evidence for the rate of apoptosis in inflammatory neutrophils being continually modulated by death and survival signals in the inflammatory milieu. This allows for rapid resolution of inflammation as levels of survival factors fall, and suggests new strategies for inducing resolution of inflammation. J. Leukoc. Biol. 67: 662–668; 2000.
Expression of genes involved in initiation, regulation, and execution of apoptosis in human neutrophils and during neutrophil differentiation of HL-60 cells
Authors: Santos-Beneit Antonio M , Mollinedo Faustino 
Published: January 2018

Abstract
Neutrophils possess a very short lifespan, dying by apoptosis. HL-60 cells undergo apoptosis after neutrophil differentiation with dimethyl sulfoxide (DMSO). We have found that the onset of apoptosis in neutrophil-differentiating HL-60 cells correlates with the achievement of an apoptosis-related gene expression pattern similar to that of peripheral blood mature neutrophils. Using reverse transcriptase-polymerase chain reaction, cloning, and sequencing techniques, we have found that HL-60 cells express bak, bik, bax, bad, bcl-2, bcl-xL, bcl-w, bfl-1, fas, and caspases 1–4 and 7–10. After DMSO treatment, bak, bcl-w, bfl-1, fas, and caspases 1 and 9 were up-regulated, whereas bik, bcl-2, and caspases 2, 3, and 10 were down-regulated at different degrees, achieving mRNA expression levels that correlated with those detected in peripheral blood neutrophils. Caspase-2 mRNA and protein expression was drastically reduced after HL-60 cell differentiation, being absent in both HL-60-differentiated neutrophils and mature neutrophils, whereas caspase-3 and -10 mRNA and protein expression were diminished upon HL-60 cell differentiation until achieving the respective levels found in mature neutrophils. Bak and bfl-1 mRNA levels were largely increased during DMSO-induced differentiation of HL-60 cells, and these genes were the bcl-2 family members that were expressed most abundantly in mature neutrophils. Bcl-2 overexpression or caspase inhibition prevented differentiation-induced apoptosis in HL-60 cells, but not their differentiation capability. Neutrophil spontaneous apoptosis was also blocked by the caspase inhibitor z-Asp-2, 6-dichlorobenzoyloxymethylketone. Peripheral blood neutrophils expressed bak, bad, bcl-w, bfl-1, fas, and caspases 1, 3, 4, and 7–10, but hardly expressed bcl-2, bcl-xL, bik, bax, and caspase-2. These results suggest that the above gene expression changes in neutrophil-differentiating HL-60 cells may play a role in the acquisition of the neutrophil apoptotic features. J. Leukoc. Biol. 67:712–724; 2000.
Dexamethasone promotes phagocytosis and bacterial killing by human monocytes/macrophages in vitro
Authors: van der Goes Annette , Hoekstra Karin , van den Berg Timo K , Dijkstra Christine D 
Published: January 2018

Abstract
One of the actions of glucocorticoids (GC) in multiple sclerosis (MS) is an inhibitory effect on demyelination. This can be caused by a reduction in the number of infiltrating macrophages and/or by an effect on the phagocytosis of myelin. Here we investigate the effect of GC on the phagocytosis of myelin. Contrary to what was expected, we found that incubation of human monocytes with dexamethasone (DEX) for 48 h augmented (approximately threefold) the phagocytosis of myelin. This enhancement of phagocytosis by human monocytes was not restricted to myelin. Phagocytosis of various particles mediated by different macrophage receptors was increased by DEX. We found that not only the phagocytosis of Staphylococcus aureus bacteria was augmented, but also the killing of these bacteria was at least twice as effective after culture with DEX. Tumor necrosis factor α production of human monocyte-derived macrophages induced by lipopolysaccharide and S. aureus was suppressed by DEX. Together our results show that DEX promotes the phagocytosis of particles by human monocytes and thereby may contribute to tissue repair after immune-mediated tissue damage or infection. These data shed a new light on the clinical application of GC. J. Leukoc. Biol. 67: 801–807; 2000.
Involvement of glutamine, arginine, and polyamines in the action of ornithine α-ketoglutarate on macrophage functions in stressed rats
Authors: Moinard Christophe , Caldefie Florence , Walrand Stephane , Felgines Catherine , Vasson Marie-Paule , Cynober Luc 
Published: January 2018

Abstract
The ability of ornithine α-ketoglutarate (OKG) to enhance macrophage cytotoxicity in stress situations has been described, but the mechanisms involved remain unclear. It is known that OKG administration generates glutamine (GLN), arginine (ARG), and polyamines. This study will (1) evaluate the effect of OKG on tumor necrosis factor α (TNF-α) secretion and nitric oxide (NO) production in macrophages from glucocorticoid (DEX)-treated rats, and determine whether these effects can be reproduced by GLN or ARG supplementations, and (2) use in vivo metabolic inhibitors methionine sulfoximine (inhibitor of GLN synthetase), S-methylthiourea (inhibitor of inducible nitric oxide synthase), and difluoromethylornithine (inhibitor of ornithine decarboxylase) to assess the roles of GLN, ARG, and polyamines in OKG action. Controls a mixture of nonessential amino acids (NEAA). GLN, ARG, and OKG all restored TNF-α secretion by macrophages of glucocorticoid-treated rats. The same results were obtained with GLN and ARG supplementation. However, the use of inhibitors clearly showed that OKG does not modulate TNF-α secretion by GLN, ARG, or polyamine pathways. We also observed that OKG enhanced NO release by stimulated macrophages (DEX-OKG, 1.77 ± 0.64 vs. DEX-NEAA, 0.29 ± 0.29 nmol/106 cells, P &lt; 0.05). Using inhibitors, it appears that this action of OKG is probably mediated via polyamine synthesis and GLN. However, an oral administration of an equimolar amount of GLN failed to reproduce the OKG-mediated effect, possibly because OKG generates more GLN in the systemic circulation than GLN itself when these substances are given orally. Our results underline the complexity of the mechanism of action of OKG, which can differ according to the functions of even a single cell type. J. Leukoc. Biol. 67: 834–840; 2000.
Positive Psychology Factors as Predictors of Latina/o College Students’ Psychological Grit
Authors: Vela Javier Cavazos , Smith Wayne D. , Whittenberg James F. , Guardiola Rebekah , Savage Miranda 
Published: January 2018

Latina/o college students (N= 130) provided perceptions of psychological grit, presence of meaning in life, search for meaning in life, hope, life satisfaction, and mindfulness. Hope and mindfulness were significant predictors of psychological grit. A discussion regarding the importance of these findings and implications for counselors are presented.Un grupo de estudiantes universitarios latinos (N= 130) aportó sus percepciones de perseverancia psicológica, presencia de sentido en la vida, búsqueda de sentido en la vida, esperanza, satisfacción vital y atención plena. Se presenta una discusión sobre la importancia de estos hallazgos y sus implicaciones para los consejeros.
Early detection of myocardial involvement by T1 mapping of cardiac MRI in idiopathic inflammatory myopathy
Authors: Yu Liuyu , Sun Jianhong , Sun Jiayu , Li Jiangbo , Dong Yang , Zhou Xiaoyue , Greiser Andreas , Han Yuchi , Zhang Qing , Xie Qibing , Chen Yucheng 
Published: January 2018

BackgroundPolymyositis (PM) and dermatomyositis (DM) are common types of idiopathic inflammatory myopathy (IIM), wherein patients are prone to adverse cardiovascular events.PurposeTo explore the value of cardiac magnetic resonance imaging (MRI) for detecting cardiac involvement in PM/DM patients using a T1 mapping technique.Study TypeProspective observational study.PopulationIn all, 25 PM/DM patients free of cardiovascular symptoms and preserved ventricular systolic function and 25 healthy volunteers matched for age and sex served as controls.Field Strength/SequenceCardiac MRI at 3T, including steady‐state free precession (SSFP) cine imaging, late gadolinium enhancement (LGE), and T1 mapping with modified Look–Locker inversion recovery (MOLLI).AssessmentMyocardial native T1 and extracellular volume (ECV) of the left ventricle as well as the correlations with disease activity were analyzed.Statistical TestsIndependent sample's t‐test, Fisher's exact test, or chi‐square test, Pearson's correlation (r) were applied. P ≤ 0.05 was considered significant.ResultsLeft ventricular end‐diastolic/end‐systolic volume index (P = 0.643, P = 0.325, respectively), mass index (P = 0.719), and ejection fraction (P = 0.144) were not significantly different between PM/DM patients and controls. LGE was found in 19% of PM/DM patients and none of the control subjects. PM/DM patients showed significantly higher native T1 values (1263.7 ± 84.0 msec vs. 1200.6 ± 43.0 msec, P = 0.002) and expanded extracellular volume (ECV) (32.6 ± 3.7% vs. 26.7 ± 2.3%, P < 0.001) compared with control subjects. ECV values in PM/DM patients had a high proportion (60%) over the 95% percentile of normal controls. Meanwhile, there was a significant correlation between native T1 (r = 0.710, P = 0.0001) or ECV (r = 0.508, P = 0.01) and N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP).Data ConclusionT1 mapping of cardiac MRI is valuable to detect subclinical myocardial involvement in PM/DM patients, and both myocardial native T1 and ECV could serve as early imaging markers for myocardial impairment in PM/DM.Level of Evidence: 2Technical Efficacy: Stage 3J. MAGN. RESON. IMAGING 2018;48:415–422.