bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-4 and CD40 ligation affect differently the differentiation, maturation, and function of human CD34+ cell-derived CD1a+CD14− and CD1a−CD14+ dendritic cell precursors in vitro
Authors: Canque Bruno , Camus Sandrine , Yagello Micael , Gluckman Jean Claude 
Published: January 2018

Abstract
We examined the effect of interleukin (IL)-4 or CD40 ligation on the differentiation and maturation of CD1a+CD14– and CD1a–CD14+ dendritic cell (DC) precursors. Cord blood CD34+ cells were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor α (TNF-α), to which stem cell factor and Flt-3 ligand were added for 5 days. Phenotypic analysis of DC precursors on culture day 7 showed that CD1a+CD14– cells expressed higher CD11c and CD80 levels and lower CD116/GM-CSFR and CCR-5 levels than their CD1a–CD14+ counterparts. Culturing CD1a+CD14– precursors with GM-CSF and TNF-α resulted in DC with heterogeneous CD1a, HLA;SMDR (DR), CD11b, and CD83 expression, 10% of which acquired CD14. IL-4 and CD40 ligation affected their differentiation in contrasting ways: IL-4 induced CD1ahiCD14– DRloCD11b+CD83–S100+ DC with reduced MLR-stimulating capacity, whereas CD40 ligation led to CD1alo/-CD14–CD40–DRhiCD11b–CD83+S100+/– DC with stronger MLR-stimulating capacity. Also, both IL-4 and CD40 ligation promoted RelB expression and nuclear translocation. When CD1a–CD14+ precursors were maintained in only the presence of GM-CSF and TNF-α, this led to mixed populations of adherent macrophages and nonadherent CD1a–CD14+ monocytes, and of CD1a+CD14– and CD1a+CD14+ DC, which were DRloCD11b+-CD83–S100–. IL-4 or CD40 ligation prevented their differentiation into macrophages and resulted in DC with phenotypes close to those issued from CD1a+CD14– precursors, with only a minority staying CD14+ but most being S100–; their MLR-stimulating capacity also increased but remained lower than that of DC differentiated from CD1a+CD14– precursors. Thus, IL-4 or CD40 ligation induced CD1a+CD14– and CD1a–CD14+ DC precursors to differentiate into phenotypically close but functionally different DC populations, suggesting that DC function is primarily determined by their origin. The heterogeneity of DC should then be related to different developmental pathways and to different stages of maturation/activation. J. Leukoc. Biol. 64: 235–244; 1998.
Combinatorial requirements for adhesion molecules in mediating neutrophil emigration during bacterial peritonitis in mice
Authors: Mizgerd Joseph P , Quinlan William M , LeBlanc Brian W , Kutkoski Gregory J , Bullard Daniel C , Beaudet Arthur L , Doerschuk Claire M 
Published: January 2018

Abstract
To investigate the requirements for adhesion molecules in neutrophil emigration during peritonitis, mice received intraperitoneal injections of Streptococcus pneumoniae while the functions of multiple adhesion molecules were blocked. Emigration after 4 h was compromised by antibodies against ICAM-1 or genetic deficiency of ICAM-1. Anti-CD11a/CD18 antibodies decreased emigration in ICAM-1 mutant mice, suggesting that ICAM-1 independent emigration requires CD11/CD18 complexes. In contrast, mice mutant in ICAM-1 plus E-selectin showed no defect in emigration, suggesting that E-selectin commits neutrophils to an ICAM-1-dependent pathway during streptococcal peritonitis. However, in mutant mice lacking the three endothelial adhesion molecules E-selectin, P-selectin, and ICAM-1, emigration after 4 h was significantly compromised. Thus, P-selectin is essential to ICAM-1-and E-selectin-independent acute peritoneal inflammation. After 24 h of peritonitis, there were no differences between WT and E-selectin/P-selectin/ICAM-1 mutant mice, demonstrating that these endothelial adhesion molecules are not essential to neutrophil emigration during later stages of peritonitis. J. Leukoc. Biol. 64: 291–297; 1998.
A 70-kDa amino-terminal fibronectin fragment supports gelatin binding to macrophages and decreases gelatinase activity
Authors: Penc Stanley F , Blumenstock Frank A , Kaplan John E 
Published: January 2018

Abstract
We previously reported that a macrophage response that increased binding to 125I-radiolabeled soluble denatured collagen (gelatin) was induced by preincubation of macrophage with a 70-kDa amino-terminal fibronectin fragment and soluble nonlabeled gelatin [S. F. Penc, F. A. Blumenstock, J. E. Kaplan (1995) J. Leukoc. Biol. 58, 501–509]. We now report that neither protein synthesis nor recycling of receptors between the cell surface and interior were required for this response. However, removal of cell surface components with trypsin demonstrated that induced gelatin binding required native cell surface constituents. It was found that in the presence of the 70-kDa fibronectin fragment and gelatin, matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) activity in the cell layers was significantly decreased or undetectable, respectively. Similar levels of increased gelatin binding could be reproduced after inhibition of matrix-degrading metalloprotease activity with 1′10-phenanthroline. These results demonstrate that a macrophage specific response that decreased gelatinase activity and increased gelatin binding was initiated by interaction with a 70-kDa fibronectin fragment and gelatin. J. Leukoc. Biol. 64: 351–357; 1998.
IL-4 and a glucocorticoid up-regulate CXCR4 expression on human CD4+ T lymphocytes and enhance HIV-1 replication
Authors: Wang Jianbin , Harada Akihisa , Matsushita Shuzo , Matsumi Shintaro , Zhang Yi , Shioda Tatsuo , Nagai Yoshiyuki , Matsushima Kouji 
Published: January 2018

Abstract
CXCR4 is a key co-receptor required for the infection of T-tropic HIV-1 strain of CD4+ T lymphocytes. The regulation of this chemokine receptor was therefore studied. Th2 polarized cells expressed more CXCR4 than Th1 cells. Among a panel of cytokines and stimulants, a Th2 type cytokine interleukin-4 (IL-4) selectively up-regulated the mRNA level as well as surface protein expression of CXCR4 within 16 h. In addition, CXCR4 was also up-regulated by a glucocorticoid, dexamethasone. These treated cells became more responsive in transendothelial migration assays to the specific CXCR4 ligand, SDF-1α. Furthermore, up-regulation of CXCR4 was also associated with the enhancement of HIV replication in human CD4+ T lymphocytes. This study indicates the enhanced T-tropic HIV-1 infection to CD4+ T lymphocytes through up-regulation of CXCR4 by several immunomodulating agents, IL-4, and a glucocorticoid. These findings may explain the shift to T-tropic HIV-1 dominance during AIDS progression when Th2 comes to predominate. J. Leukoc. Biol. 64: 642–649; 1998.
Platelet-activating factor induces a concentration-dependent spectrum of functional responses in bovine neutrophils
Authors: Swain Steve D , Bunger Peggy L , Sipes Karen M , Nelson Laura K , Jutila Kathryn L , Boylan Shane M , Quinn Mark T 
Published: January 2018

Abstract
We characterized the dose response of bovine neutrophils to platelet-activating factor (PAF) with respect to the following functions: calcium flux and membrane potential changes, actin polymerization, degranulation, and the production and/or priming of the oxidative burst. PAF at very low concentrations (10 and 10 M) caused changes in intracellular calcium and membrane potential in bovine neutrophils, whereas moderate PAF concentrations (≥10–7 M) resulted in increased actin polymerization. Degranulation responses to PAF were more complex: low concentrations (10–9 M) caused secretory granule degranulation, moderate doses (≥ 10–7 M) caused specific granule degranulation, whereas azurophil degranulation only occurred at high (10–5 M) PAF concentrations. Treatment of bovine neutrophils with PAF at concentrations ≥10–7 M also caused up-regulation of the adhesion molecules Mac-1 and L-selectin. PAF stimulation resulted in a very weak [compared to phorbol myristate acetate (PMA)] oxidative burst in bovine neutrophils, and only at high (10–6 M) concentrations. Unlike human neutrophils, bovine neutrophils were poorly primed by PAF treatment. Only high concentrations of PAF (10–5 M) caused an increased rate of PMA-stimulated superoxide production, although lower doses of PAF did reduce the lag time preceding the PMA-induced oxidative burst. The overall pattern that can be inferred is that lower concentrations of PAF promote neutrophil sensitivity and interaction by selective degranulation, up-regulation of adhesion molecules, and increased actin polymerization. In contrast, higher PAF concentrations can promote, albeit weakly, more direct bactericidal responses, such as the release of reactive oxygen species and granule enzymes. The ability of PAF to modulate a graded response in bovine neutrophils would allow the cell to respond proportionally to the severity of a stimulus. J. Leukoc. Biol. 64: 817–827; 1998.
Anti-human RP105 sera induces lymphocyte proliferation
Authors: Roshak Amy K , Anderson Karen M , Holmes Stephen D , Jonak Zdenka , Bolognese Brian , Terrett Jonathan , Marshall Lisa A 
Published: January 2018

Abstract
Cellular environment dictates whether antigen binding to the B lymphocyte receptor together with co-stimulatory molecules will result in proliferation, anergy, or apoptosis. Murine RP105 is a member of the leucine-rich repeat family of proteins, which is specifically expressed on mature B cells. Monoclonal antibodies to the murine RP105 induce proliferation and protect B cells from apoptosis, suggesting an important regulatory role in murine B lymphocyte function. We identified a human RP105 homolog and mapped the gene to chromosome 5q 12.3-13.1. Tissue distribution analysis shows that the transcript is found predominately in lymphoid tissues including spleen, tonsils, appendix, and peripheral blood leukocytes. Polymerase chain reaction analysis of isolated primary human cell populations confirms that mRNA exists in spleen B lymphocytes and monocytes but not T lymphocytes. Western blot analysis demonstrates specific expression of human RP105 in human B lymphocytes. Murine anti-human RP105 sera was generated using DNA immunization. The antisera contained antibodies that recognized and bound to human B lymphocytes from both spleen and peripheral blood as assessed by flow cytometry. Assessment of biological function showed that human peripheral blood leukocytes incubated with anti-RP105 sera were induced to proliferate as measured by tritiated thymidine incorporation. Moreover, anti-CD40 and interleukin-4-treated cells but not those exposed to anti-RP105 sera produced soluble CD23, suggesting distinct functional roles. This is the first demonstration of both the existence of RP105 protein on human B lymphocytes and its role in the regulation of B lymphocyte activation. J. Leukoc. Biol. 65: 43–49; 1999.
Regulation of IL-8RA (CXCR1) expression in polymorphonuclear leukocytes by hypoxia/reoxygenation
Authors: Grutkoski P S , Graeber C T , D'Amico R , Keeping H , Simms H H 
Published: January 2018

Abstract
Interleukin-8 (IL-8) is an important mediator of neutrophil (PMN) function and the type A IL-8 receptor (IL-8RA) mediates these pro-inflammatory signals. Hypoxia or hypoxia/reoxygenation (H/R) affects the production of IL-8, but no data is available regarding its effect on IL-8RA expression. The purpose of this study was to determine the effects of hypoxia and/or H/R on the expression of IL-8RA in PMN. We demonstrated that IL-8RA mRNA levels were similar under normoxic and hypoxic conditions but H/R resulted in a significant reduction in mRNA expression between 30 and 60 min. IL-8RA protein also decreased with reoxygenation of whole blood, which was altered by the addition of specific antioxidants. Therefore, H/R appears to attenuate the effect of IL-8 by down-regulating IL-8RA in PMN. These data show that changes in oxygen tension within the wound site not only affect the expression of inflammatory cytokines, but also control their actions by regulating their receptors. J. Leukoc. Biol. 65: 171–178; 1999.
Leukocyte subsets and neutrophil function after short-term spaceflight
Authors: Stowe Raymond P , Sams Clarence F , Mehta Satish K , Kaur Indreshpal , Jones Michael L , Feeback Daniel L , Pierson Duane L 
Published: January 2018

Abstract
Changes in leukocyte subpopulations and function after spaceflight have been observed but the mechanisms underlying these changes are not well defined. This study investigated the effects of short-term spaceflight (8–15 days) on circulating leukocyte subsets, stress hormones, immunoglobulin levels, and neutrophil function. At landing, a 1.5-fold increase in neutrophils was observed compared with preflight values; lymphocytes were slightly decreased, whereas the results were variable for monocytes. No significant changes were observed in plasma levels of immunoglobulins, cortisol, or adrenocorticotropic hormone. In contrast, urinary epinephrine, norepinephrine, and cortisol were significantly elevated at landing. Band neutrophils were observed in 9 of 16 astronauts. Neutrophil chemotactic assays showed a 10-fold decrease in the optimal dose response after landing. Neutrophil adhesion to endothelial cells was increased both before and after spaceflight. At landing, the expression of MAC-1 was significantly decreased while L-selectin was significantly increased. These functional alterations may be of clinical significance on long-duration space missions. J. Leukoc. Biol. 65: 179–186; 1999.
Functional deficiencies of peritoneal cells from gene-targeted mice lacking G-CSF or GM-CSF
Authors: Zhan Yifan , Basu Sunanda , Lieschke Graham J , Grail Dianne , Dunn Ashley R , Cheers Christina 
Published: January 2018

Abstract
Gene-targeted mice lacking the hemopoietic growth factors, granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage (GM)-CSF, show increased susceptibility to infection with the facultative intracellular bacterium, Listeria monocytogenes. The resident peritoneal cell populations from G-CSF-/- and GM–CSF-/- mice showed reduced production of the bactericidal molecule nitric oxide. Macrophage-mediated tumoricidal activity and phagocytosis of Listeria were reduced in G-CSF-/-, but not in GM-CSF-/-, mice. In G-CSF-/- mice, there was an unexpected expansion (from 18% in WT to 38%) of a population of cells with morphology intermediate between typical macrophages and typical lymphocytes. These cells had some of the features of poorly differentiated macrophages, being adherent to plastic but poorly phagocytic, nonspecific esterase positive but myeloperoxidase negative. They were largely negative for the macrophage marker F4/80 and for Thy1, B220, and Gr1. Their disproportionate presence, and the corresponding deficiency in typical macrophages, possibly accounts for some of the functional deficiencies observed in G-CSF-/- mice. J. Leukoc. Biol. 65: 256–264; 1999.
Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides
Authors: Simões Sergio , Slepushkin Vladimir , Pretzer Elizabeth , Dazin Paul , Gaspar Rogério , de Lima Maria C Pedroso , Düzgüneş Nejat 
Published: January 2018

Abstract
The crucial function of macrophages in a variety of biological processes and pathologies render these cells important targets for gene therapeutic interventions. Commonly used synthetic gene delivery vectors have not been successful in transfecting these non-dividing cells. A combination strategy involving cationic liposomes to condense and carry DNA, transferrin to facilitate cellular uptake, and the pH-sensitive peptide GALA to promote endosome destabilization, resulted in significant expression of a luciferase gene. Transfection of macrophages was dependent on the degree of differentiation of the cells. The quaternary complexes of cationic liposomes, DNA, transferrin, and GALA exhibited a net negative charge, which may obviate a limitation of cationic synthetic vectors in vivo. The lack of cytotoxicity and the expected lack of immunogenicity of these complexes may render them useful for gene delivery to macrophages in vivo. J. Leukoc. Biol. 65: 270–279; 1999.
Induction of NOS in rat blood PMN in vivo and in vitro: modulation by tyrosine kinase and involvement in bactericidal activity
Authors: Fierro Iolanda M , Nascimento-DaSilva Vany , Arruda Maria Augusta B , Freitas Marta S , Plotkowski Maria Cristina , Cunha Fernando Q , Barja-Fidalgo Christina 
Published: January 2018

Abstract
Intravenous administration of lipopolysaccharide (LPS) to rats increased the production of nitric oxide (NO) metabolites (NOx) by blood polymorphonuclear neutrophils (PMN) in vitro. Both dexamethasone and L-NMMA, added in vitro to neutrophil cultures, inhibited the production of NO. On the other hand, the production of NO was not affected by the treatment, in vivo or in vitro, with different inhibitors of cyclooxygenase or 5-lipoxygenase or with a platelet-activating factor (PAF) antagonist. The incubation of blood PMN from normal rats in vitro with neutrophil activators (PAF, leukotriene B4, and interleukin-8) and different cytokines [interleukin-1, tumor necrosis factor α, and interferon-γ (IFN-γ)] showed that only IFN-γ was able to induce the production of high amounts of NO. This induction was directly correlated with the expression of iNOS and an increase in in the enzyme activity in blood PMN. The tyrosine kinase inhibitor genistein inhibited NO production induced by IFN-γ, suggesting that the signal transduction pathway leading to NOS induction in rat PMN involves phosphorylation by tyrosine kinase. We also showed that NO produced by IFN-γ activated rat blood PMN involved in the killing of Pseudomonas aeruginosa. J. Leukoc. Biol. 65: 508–514; 1999.
Cbl functions downstream of Src kinases in FCγRI signaling in primary human macrophages
Authors: Erdreich-Epstein Anat , Liu Ming , Kant Anita M , Izadi Kayvon D , Nolta Jan A , Durden Donald L 
Published: January 2018

Abstract
Cbl is a cytosolic protein that is rapidly tyrosine phosphorylated in response to Fc receptor activation and binds to the adaptor proteins Grb2, CrkL, and Nck. A few reports describe Cbl interactions in primary human hematopoietic cells. We show evidence that Cbl participates in signaling initiated by FcγRI receptor cross-linking in human primary macrophages, and functions downstream of Src family kinases in this pathway. FcγRI stimulation in human macrophages was associated with rapid and transient tyrosine phosphorylation of the Cbl adaptor protein. Immunoprecipitated Cbl was complexed with several tyrosine phosphorylated proteins, the most prominent of which was a 38-kDa band identified as the CrkL adaptor protein. CrkL associated with tyrosine-phosphorylated Cbl and itself became tyrosine phosphorylated after FcγRI cross-linking. SLP-76, a recently cloned Grb2-associated protein, was strongly tyrosine phosphorylated after FcγRI stimulation and was associated with both Cbl and Grb2. Grb2 and Cbl binding to SLP-76 were inducible after FcγRI stimulation of the macrophages. Nck was inducibly bound to Cbl after FcγRI stimulation, whereas Grb2 was constitutively associated with it. Shc was also inducibly tyrosine phosphorylated and bound to Grb2 after FcγRI stimulation of the macrophages. PP1, a specific inhibitor of Src kinases, inhibited the FcγRI-induced respiratory burst, as well as the tyrosine phosphorylation of Cbl and its inducible association with CrkL. These results suggest a fundamental role for the tyrosine phosphorylation of Cbl, CrkL, SLP-76, and Shc and the association of Cbl with CrkL, SLP-76, and Nck in FcγRI signaling in human macrophages. Experiments performed with PP1, the specific Src kinase inhibitor, demonstrate the first evidence that Cbl and the Cbl-Crkl interaction are downstream targets for myeloid Src kinases required for the activation of myeloid NADPH oxidase activity. J. Leukoc. Biol. 65:523–534; 1999.
The taming of IL-12: suppressing the production of proinflammatory cytokines
Authors: Sutterwala Fayyaz S , Mosser David M 
Published: January 2018

Abstract
Interleukin (IL)-12 is a cytokine that possesses both proinflammatory and immunoregulatory activity. IL-12, and the interferon-γ (IFN-γ) that is induced by IL-12, play central roles in the development of the Th1-type immune responses that are required for immunity to intracellular pathogens. Recently a number of these pathogens, including Leishmania, measles virus, and human immunodeficiency virus (HIV), have been shown to subvert the development of cell-mediated immunity by actively inhibiting the production of IL-12. Similarly, the ligation of phagocytic receptors on macrophages has also been shown to suppress IL-12 production. The suppression of IL-12 production by receptor ligation occurs by at least two distinct mechanisms: one involves a direct inhibition of gene transcription and the other depends on the production of inhibitory cytokines. We review studies in which IL-12 has been experimentally manipulated, and we compare the mechanisms by which this regulation can occur. Because the IL-12 that is produced during acute inflammation and chronic autoimmune disorders can lead to exacerbated disease, the development of pharmacological means to suppress IL-12 production is currently under investigation. This review focuses on the production of IL-12 by antigen-presenting cells and the methods by which the down-regulation of IL-12 production can be exploited either by pathogens or for therapeutic ends. J. Leukoc. Biol. 65: 543–551; 1999.
Morphine modulation of peritoneal inflammation in Atlantic salmon and CB6 mice
Authors: Chadzinska M , Kolaczkowska E , Seljelid R , Plytycz B 
Published: January 2018

Abstract
Peritoneal inflammation is a convenient model for comparisons of modulatory effects of morphine in phylogenetically distant vertebrates. Both in salmon and mice morphine injected intraperitoneally together with an irritant (thioglycollate) significantly inhibits inflammation as estimated by the number of peritoneal leukocytes. The low number of exudate cells in morphine-treated animals seems to be compensated by their high activity, as evidenced by the enhanced phorbol myristate acetate-induced respiratory burst. The morphine-inhibited influx of leukocytes into the irritated peritoneal cavity correlates with the morphine-lowered level of plasma chemotactic factors both in fish and mice. It implies that morphine impairs the level of plasma chemotactic factor either directly (affecting their release from the resident peritoneal cells) or indirectly (decreasing the number of inflammatory leukocytes by inhibition of their migration from hemopoietic sites). The inhibitory effects of morphine on both the cell number and chemoattractant level are completely reversed by the naltrexone pretreatment, which implicates the involvement of opioid receptors. J. Leukoc. Biol. 65: 590–596; 1999.
Influenza A virus up-regulates neutrophil adhesion molecules and adhesion to biological surfaces
Authors: Hartshorn Kevan L , White Mitchell R 
Published: January 2018

Abstract
Influenza A virus (IAV) binds to sialylated neutrophil surface components (e.g., CD43 and sialyl Lewisx antigen) and induces both activation and functional depression of neutrophils. We report that IAV enhanced neutrophil adhesion to surfaces coated with serum or serum components, but not to uncoated plastic. IAV up-regulated expression of integrins (CD11b and CD11c) and carcinoembryonic-related antigens on neutrophils, while reducing expression of CD43, L-selectin, and P-selectin glycoprotein ligand (PSGL). Although treatment of neutrophils with elastase or O-sialoglycoprotease decreased surface CD43 and PSGL, they did not reduce binding of IAV to neutrophils, implying that IAV can bind to alternate binding sites in the absence of CD43. Pretreatment of neutrophils with elastase also did not prevent IAV from increasing expression of integrins and enhancing adhesion. Up-regulation of adhesion molecules and adhesion are important, previously unrecognized, features of neutrophil activation by IAV. Further studies will be needed to clarify the mechanism of these effects. J. Leukoc. Biol. 65: 614–622; 1999.