bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maturation decreases responsiveness of human bone marrow B lineage cells to stromal-derived factor 1 (SDF-1)
Authors: Fedyk Eric R , Ryan Daniel H , Ritterman Ion , Springer Timothy A 
Published: January 2018

Abstract
We compared the chemotactic responsiveness of different subsets of human B lineage cells to stromal derived factor-1 (SDF-1). High percentages (30–40% of input) of purified bone marrow progenitors including non-B lineage progenitors, pro-B cells, and pre-B cells migrated to SDF-1α, demonstrating that SDF-1 is an efficacious chemoattractant of these cells. Pro-B cells responded optimally to a lower concentration of SDF-1 than other subsets, demonstrating that SDF-1 is a more potent chemoattractant of this subset. A lower percentage (10–15% of input) of mature B lymphocytes migrated to SDF-1α than pro-B cells, demonstrating that responsiveness of B lineage cells to SDF-1 decreases during differentiation. Inhibition by anti-CXCR4 mAb demonstrated that migration of B lineage cells to SDF-1 was completely dependent on CXC chemokine receptor-4 (CXCR4). Mature B cells expressed higher levels of CXCR4 receptors than uncommitted progenitors and pro-B cells, despite differences in responsiveness to SDF-1. CXCR4 receptors expressed by unresponsive and SDF-1-responsive B cells bound SDF-1a with similar affinities (K D= 1.7–3.3 × 10−9 M). Therefore, elements downstream from CXCR4 appear to regulate responsiveness of B cells to SDF-1. We speculate that SDF-1 and CXCR4 direct migration of progenitor cells in microenvironments that promote B lymphopoiesis. J. Leukoc. Biol. 66: 667–673; 1999.
ATP receptors and giant cell formation
Authors: Di Virgilio Francesco , Falzoni Simonetta , Chiozzi Paola , Sanz Juana M , Ferrari Davide , Buell Gary N 
Published: January 2018

Abstract
We have investigated the role of the purinergic P2X7 receptor in the formation of multinucleated giant cells in human monocyte/macrophage cultures stimulated with either concanavalin A or phytohemagglutinin. Macrophage fusion can be blocked by a P2X7-selective pharmacological antagonist or by a mAb directed against the extracellular P2X7 domain. Furthermore, macrophage cell clones expressing high P2X7 levels spontaneously fuse in culture, whereas macrophage clones lacking P2X7 are unable to fuse. Our findings suggest that the newly identified purinergic P2X7 receptor plays a central role in the complex chain of events leading to generation of macrophage-derived giant cells. J. Leukoc. Biol. 66: 723–726; 1999.
Differential effects of B7-1 and B7-2 on the costimulation of mouse nonspecific cytotoxic T lymphocyte development in response to anti-CD3 antibody
Authors: Makrigiannis Andrew P , Musgrave Bruce L , Hoskin David W 
Published: January 2018

Abstract
Despite extensive study, the relative contribution of B7-1 and B7-2 molecules to the costimulation of cytotoxic T lymphocyte (CTL) activation remains controversial. We used blocking mAbs to B7-1 and B7-2 molecules to determine the role of these B7 family members in the in vitro induction of mouse nonspecific CTL in response to soluble anti-CD3 mAb. Optimal induction of anti-CD3-activated killer-T (AK-T) cells was found to require interactions with B7-2 on residual accessory cells in nylon wool-nonadherent spleen cell preparations during the first 12 h of culture in the presence of anti-CD3 mAb. Because B7-1 is not expressed at high enough levels on residual accessory cells in primary T cell cultures to be an effective ligand for CD28, we used LPS-stimulated B cells, which express substantial B7-1, in addition to B7-2, to determine the contribution of B7-1 to AK-T cell development. Compared with B7-2, the contribution of B7-1 to the costimulation of AK-T cells in this system was modest because anti-B7-1 mAb had only a minimal inhibitory effect on the generation of cytotoxicity, whereas anti-B7-2 mAb strongly inhibited AK-T cell development. Anti-CD3-induced cytotoxicity of T cells from CD4 knockout mice and CD4-depleted nylon wool-nonadherent spleen cells from wild-type mice was inhibited by anti-B7-2 mAb, implying that B7-2 is able to bind directly to CD28 on CD8+ T cells and costimulate their activation. B7-1 blockade, on the other hand, did not affect the costimulation of CD8+ T cells. Blockade of B7-2/CD28 interactions with anti-B7-2 mAb strongly inhibited granzyme B, but not perforin or Fas ligand gene expression, suggesting an explanation for the inhibitory effect of anti-B7-2 mAb on AK-T cell development. These data indicate that B7-2 is superior to B7-1 as a costimulator of mouse AK-T cell induction. J. Leukoc. Biol. 66: 792–802; 1999.
Modulatory effects of human herpes virus-7 on cytokine synthesis and cell proliferation in human peripheral blood mononuclear cell cultures
Authors: Atedzoé Blanche Ngola , Menezes José , D'Addario Mario , Xu Jingwu , Ongradi Joseph , Ahmad Ali 
Published: January 2018

Abstract
Human herpes virus-7 (HHV-7) infects cells of the immune system and thus may modulate their function. To investigate the potential immunomodulatory effects of this virus, we performed an in vitro study in which we investigated effects of HHV-7 on the synthesis of several key immunomodulatory cytokines, i.e. tumor necrosis factor α (TNF-α), interleukin-2 (IL-2), interferon-γ (IFN-γ), IL-4, IL-6, and transforming growth factor β (TGF-β). This was examined after in vitro infection of human peripheral blood mononuclear cells (PBMC) with HHV-7. We found elevated levels of TNF-α, TGF-β, and IFN-γ in the supernatants of HHV-7-infected cells. By reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, using cytokine-specific primers, we found that levels of TNF-α, TGF-β, and IFN-γ mRNA were increased in the infected cells. The HHV-7 infection also significantly (P &lt; 0.05) decreased the production of IL-2 from activated, IL-2-producing PBMC. Furthermore, mitogen- and cytokine-induced cellular proliferative responses of human PBMC were found to be significantly (P &lt; 0.05) down-regulated by this virus. On the other hand, HHV-7 did not affect IL-4 and IL-6 synthesis. Overall, our results indicate that HHV-7 infection causes significant immunomodulatory effects with regard to cytokine synthesis in these cells as well as inhibiting lymphocyte proliferation by various stimuli. J. Leukoc. Biol. 66: 822–828; 1999.
Phosphorylation of p40-phox during activation of neutrophil NADPH oxidase
Authors: Someya Akimasa , Nunoi Hiroyuki , Hasebe Takeshi , Nagaoka Isao 
Published: January 2018

Abstract
NADPH oxidase, a superoxide-producing enzyme in phagocytic cells, consists of membrane-associated cytochrome b558 and cytosolic components (p47-phox, p67-phox, p40-phox, rac 1/2). Activation of NADPH oxidase is accompanied by the phosphorylation of cytosolic components (p47-phox and p67-phox). In this study, we have examined whether p40-phox, a newly identified cytosolic component, is phosphorylated during neutrophil activation, and the relationship between p40-phox phosphorylation and NADPH oxidase activation. When 32P-labeled guinea pig neutrophils were stimulated by phorbol 12-myristate 13-acetate, p40-phox was phosphorylated as p47-phox. It is interesting that phosphorylation of p40-phox was markedly inhibited by protein kinase C inhibitor, H-7, but not by casein kinase II inhibitor, A-3, and H-7 inhibited translocation of p40-phox and activation of NADPH oxidase. Furthermore, purified protein kinase C but not casein kinase II directly phosphorylated p40-phox of p40-phox/p47-phox/p67-phox complex. Together these observations suggest that p40-phox is phosphorylated by protein kinase C during neutrophil activation, and phosphorylation of p40-phox may be important for the activation of NADPH oxidase. J. Leukoc. Biol. 66: 851–857; 1999.
Soluble TNF-α receptors bind and neutralize over-expressed transmembrane TNF-α on macrophages, but do not inhibit its processing
Authors: Watts Alan D , Hunt Nicholas H , Madigan Michele C , Chaudhri Geeta 
Published: January 2018

Abstract
Tumor necrosis factor a (TNF-α) is initially synthesized as a type II integral membrane protein (transmembrane TNF-α) after macrophage activation. In this study we have investigated some aspects of the regulation of expression and biological activity of transmembrane TNF-α by both soluble TNF-α receptors (sTNF-αR) and inhibitors of TNF-α processing. We show, using the technique of receptor-mediated ligand precipitation (RMLP), that a dimeric construct of the type I sTNF-αR binds to transmembrane TNF-α, expressed on the mouse macrophage cell line RAW264.7, under cell culture conditions. This interaction between sTNF-αR and transmembrane TNF-α does not prevent processing and release of soluble TNF-α. A specific hydroxamic acid-based inhibitor of processing, BB1101 (British Biotech), was found to increase the total cellular levels of whole-cell, 26-kDa, precursor TNF-α by 2.2-fold. However, the inhibitor increased the levels of precursor TNF-α present solely on the cell surface (i.e., transmembrane TNF-α) by 5.1- to 7.5-fold. This increase in the levels of transmembrane TNF-α on the activated human monocytoid cell line mono mac 6 was associated with a similar (6.7-fold) increase in TNF-α-mediated cytotoxicity toward the human adenocarcinoma cell line Colo 205, which is sensitive only to the transmembrane form of TNF-α. Mono mac 6 cells, expressing transmembrane TNF-α, were found to be killing the Colo 205 target cells through apoptosis. This cytotoxicity could be neutralized by pre-incubating the mono mac 6 cells with either sTNF-αR or polyclonal anti-TNF-α serum. J. Leukoc. Biol. 66: 1005–1013; 1999.
P40phox associates with the neutrophil Triton X-100-insoluble cytoskeletal fraction and PMA-activated membrane skeleton: a comparative study with P67phox and P47phox
Authors: Benna Jamel El , Dang Pham My-chan , Andrieu Valérie , Vergnaud Sabrina , Dewas Cedric , Cachia Odile , Fay Michèle , Morel Françoise , Chollet-Martin Sylvie , Hakim Jacques , Gougerot-Pocidalo Marie-Anne 
Published: January 2018

Abstract
NADPH oxidase is an O-generating enzyme found in phagocytes such as neutrophils. It is composed of a membrane-bound cytochrome b, the cytosolic proteins p67phox, p47phox, p40phox, and the G-protein p21rac. The system is dormant in resting cells but acquires catalytic activity on exposure to appropriate stimuli. Cytochrome b, p67phox, p47phox, and rac2 associate with the cytoskeleton and membrane skeleton of activated neutrophils. It is not known whether p40phox associates with the cytoskeleton. The purpose of this study was to analyze the subcellular distribution of p40phox. When resting neutrophils were lysed in Triton X-100 or octyl glucoside buffer and separated into detergent-soluble and detergent-insoluble fractions, p40phox and p67phox were mainly associated with the detergent-insoluble fraction (defined as the cytoskeleton), whereas p47phox was mainly found in the soluble fraction. Neutrophil activation by phorbol myristate acetate (PMA) induced p47phox translocation to the cytoskeleton but did not affect the distribution of p40phox or p67phox. Using immunofluorescence confocal microscopy, we found that p40phox colocalized with filamentous actin. In neutrophils from a p67phox-deficient patient with detectable p40phox, p40phox associated with the cytoskeleton only after activation by PMA. A complex containing the three proteins was isolated from the cytoskeleton of activated neutrophils. When activated membranes were treated with Triton X-100 buffer, p40phox, p47phox, and p67phox were found in the membrane skeleton enriched in NADPH-oxidase activity; some p40phox and p47phox was found in the soluble membrane fraction, but no p67phox was detected. These findings show that p40phox, like p67phox and p47phox, binds to the cytoskeleton and membrane skeleton. In addition, p40phox can dissociate from p67phox in activated membranes. J. Leukoc. Biol. 66: 1014–1020; 1999.
Retinoid X receptor suppresses transformation by the v-myb oncogene
Authors: Šmarda Jan , Zemanová Karla , Bryja Josef , Šmardová Jana , Kozubík Alois , Hofmanová Jirina , Nemajerová Alice , Ševçíková Sabina , Kohoutek Jirí , Vodiçka Petr 
Published: January 2018

Abstract
The v-myb oncogene of avian myeloblastosis virus causes acute monoblastic leukemia in vivo and transforms myelomonocytic cells in culture. Retinoids are potent regulators of proliferation and differentiation in various cell types, and they can initiate differentiation in certain types of leukemic cells. However, the BM2 v-myb-trans-formed chicken monoblastic cell line is resistant to retinoic acid treatment. We found that overexpression of the retinoid X receptor confers sensitivity of BM2 cells to retinoic acid, resulting in induction of growth arrest and terminal differentiation. In contrast, the frequency of apoptosis was not affected by the retinoid X receptor in this cell type. We also demonstrated that suppression of transformation by v-Myb results from the negative effect of retinoid X receptor on v-Myb transactivation function, similar to that previously described for the retinoic acid receptor. The retinoid X receptor-induced inhibition of transactivation by v-Myb seems to be enhanced by a cell type-specific factor(s), which is not required by retinoic acid receptor. J. Leukoc. Biol. 66: 1039–1048; 1999.
Trp-Lys-Tyr-Met-Val-d-Met is a chemoattractant for human phagocytic cells
Authors: Bae Yoe-Sik , Kim Youndong , Kim Yong , Kim Jae Ho , Suh Pann-Ghill , Ryu Sung Ho 
Published: January 2018

Abstract
Trp-Lys-Tyr-Met-Val-d-Met (WKYMVm) is a synthetic peptide that stimulates phosphoinosi-tide (PI) hydrolysis in human leukocytes. The peptide binds to a unique cell surface receptor(s). Recently we had demonstrated that human neutrophils, monocytes, and B lymphocytes express this peptide-specific receptor and that stimulation of human leukocytes with the peptide leads to activation of the oxidative respiratory system and the bactericidal activity of neutrophils or monocytes. In this study we showed that the peptide induces chemotaxis of phagocytic leukocytes and studied the signaling pathway leading to chemotaxis in human monocytes. The peptide-induced monocyte chemotaxis is pertussis toxin (PTX)-sensitive. This fact correlates with the peptide's stimulation of PI hydrolysis and intracellular Ca2+ ([Ca2+]i) release, which is also PTX-sensitive. We demonstrate that the peptide-specific receptor is different from receptors) for monocyte chemoattractant protein-1 (MCP-1). We also show that intracellular signaling of WKYMVm leading to monocyte chemotaxis is different from that of MCP-1. The peptide-medi-ated monocyte chemotaxis is insensitive to protein kinase C (PKC) inhibitor (GF109203X) and butan-1-ol, ruling out PKC and phospholipase D participation in this process. On the other hand, a tyrosine kinase inhibitor (genistein) and RhoA inhibitor (C3 transferase) curtailed the peptide-induced chemotaxis in a concentration-dependent manner, implying the involvement of tyrosine kinase and RhoA, respectively. Treatment of human monocytes with the peptide stimulates tyrosine phosphorylation of several cellular proteins, including p125FAK and Pyk2 and translocation of RhoA from the cytosol to the membrane. We conclude that WKYMVm induces chemotaxis of human phagocytic leukocytes via unique receptors and signaling. J. Leukoc. Biol. 66:915–922; 1999.
Regulation of the processing and release of tumor necrosis factor α in a human macrophage cell line
Authors: Nakada-Tsukui Kumiko , Watanabe Naoko , Kobayashi Yoshiro 
Published: January 2018

Abstract
The proteolytic cleavage of a variety of membrane proteins, including pro-tumor necrosis factor α (pro-TNF-α), is induced by various reagents such as phorbol 12-myristate 13-acetate (PMA). In this study we generated a human macrophage cell line that constitutively produces TNF-α, and examined how the processing and release of TNF-α are regulated. The processing and release of TNF-α were enhanced by PMA through a protein kinase C-dependent pathway. Although only hy-droxamate matrix metalloproteinase (MMP) inhibitors inhibited the basal processing and release of TNF-α, the PMA-induced processing and release of TNF-α were inhibited not only by MMP inhibitors but also by 1,10-phenanthroline, 3,4-dichloroiso-coumarin (3,4-DCI), iodoacetamide, and Nα-p-tosyl-l-phenylalanine chloromethyl ketone (TPCK). Hydroxamate MMP inhibitors and 1,10-phenanthroline inhibited the processing of TNF-α on the cell surface, whereas 3,4-DCI, iodoacetamide, and TPCK inhibited the transport of TNF-α to the cell surface. These results suggest that serine and/or cysteine protease(s) may be involved in PMA-induced processing and/or transport to the cell surface. J. Leukoc. Biol. 66: 968–973; 1999.
The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granules
Authors: Cowland Jack B , Borregaard Niels 
Published: January 2018

Abstract
The in vivo mRNA levels for 16 granule proteins during neutrophil differentiation were determined to address the question of whether the synthesis of granule proteins is regulated individually or blockwise. RNA was extracted from peripheral blood granulocytes and three different populations of neutrophil precursors isolated from human bone marrow by Percoll density centrifugation. The mRNA levels in relation to the maturation of the cells were determined by Northern blot for the 12 matrix proteins myeloperoxidase, proteinase-3, elastase, defensin, lactoferrin, NGAL, hCAP-18, transcobalamin-I, SGP28, gelatinase, lysozyme, and serglycin and the 4 membrane proteins CD68, CD11b, N-formyl-methionyl-leucyl-phenylalanine receptor, and CD35. This panel of transcripts ensured that markers for all exocytosable organelles of the neutrophil were included in the study. A highly differentiated distribution of mRNAs for granule proteins was demonstrated that can explain the heterogeneity of the intracellular storage granules and secretory vesicles of the neutrophil. Furthermore, the individual distribution of these transcripts provides the basis for a more detailed assessment of neutrophil maturation than that obtained by morphological studies or the use of a single marker protein for azurophil, specific, and gelatinase granules. J. Leukoc. Biol. 66: 989–995; 1999.
Effect of age on human neutrophil function
Authors: Wenisch Christoph , Patruta Sanda , Daxböck Felix , Krause Robert , Hörl Walter 
Published: January 2018

Abstract
Neutrophil phagocytosis, reactive oxygen intermediate production (intra- and extracellular), neutrophil bactericidal activity, and chemotaxis/chemokinesis were assessed in three age groups: 21–36, 38–56, and 62–83 years. A significant age-dependent reduction in the number of phagocytized Escherichia coli per neutrophil (measured by acridine orange staining) and Staphylococcus aureus phagocytosis (measured by flow cytometry) was seen (r = 0.669 and r = 0.684, P &lt; 0.001 for both). These findings correlated with an age-dependent increase in intracellular calcium concentrations in resting neutrophils (r = 0.698, P &lt; 0.001) and a reduced hexose uptake (r = 0.591, P &lt; 0.01). In addition, a significant reduction in the intracellular reactive oxygen production was seen after stimulation with S. aureus (P &lt; 0.001) with increasing age. In contrast, no differences between the groups in reactive oxygen production was seen after stimulation with E. coli. The neutrophil bactericidal activity was impaired with increasing age (64 ± 4% of the phagocytized bacteria were killed in group 1; 66 ± 2 in group 2, and 59 ± 6 in group 3; P &lt; 0.01). In addition, a trend toward a reduced neutrophil chemotaxis was seen with increasing age (P = 0.022). The findings suggest that increased intracellular calcium concentrations in resting neutrophils and/or a reduced hexose uptake result in reduced phagocytic ability and decreased bactericidal activity of neutrophils in the elderly. J. Leukoc. Biol. 67: 40–45; 2000.
Neonatal neutrophil interaction with P-selectin: contribution of P-selectin glycoprotein ligand-1 and sialic acid
Authors: Tcharmtchi M Hossein , Smith C Wayne , Mariscalco M Michele 
Published: January 2018

Abstract
Previously we had determined that neonatal neutrophils had decreased interaction with monolayers expressing P-selectin compared to adult cells. In this study we examined the function of neonatal P-selectin glycoprotein ligand-1 (PSGL-1). A rabbit polyclonal antibody directed against the amino terminus of human PSGL-1 was produced and purified (3RB-PSGL-1). Neonatal neutrophils expressed the epitope recognized by 3RB-PSGL-1 and expression was decreased compared with adult neutrophils (20%, P &lt; 0.05). In addition neonatal neutrophils had decreased interaction with Chinese hamster ovary (CHO)-P-selectin under both shear conditions and static adhesion (P &lt; 0.05). Treatment of both neonatal and adult neutrophils with 3RB-PSGL-1 similarly inhibited the interaction with P-selectin monolayers under shear conditions, effects similar to treatment with O-sialoglycoprotein endopeptidase (OSGE). Neuraminidase treatment of neonatal and adult cells also markedly inhibited the interaction. In a detachment assay marked differences were noted between neonatal and adult cells treated with either 3RB-PSGL-1 or neuraminidase. Such treatments had little effect on adult neutrophils until shear stress exceeded 2.8 dynes/cm2. Treated neonatal neutrophils were exquisitely sensitive to shear stress with a marked decrease in interaction noted at a shear stress as low as 0.6 dynes/cm2. Thus the adhesive mechanisms that remain after treatment with neuraminidase or 3RB-PSGL-1 have a relatively low avidity and function less well in neonatal neutrophils compared to adult neutrophils. We speculate that this may account for the less efficient adhesion of neonatal neutrophils to P-selectin under conditions of flow. J. Leukoc. Biol. 67: 73–80; 2000.
CD11b/CD18-coated microspheres attach to E-selectin under flow
Authors: Crutchfield Karen L , Patil Vivek R Shinde , Campbell Craig J , Parkos Charles A , Allport Jennifer R , Goetz Douglas J 
Published: January 2018

Abstract
Neutrophils can attach to E-selectin under flow. Proposed ligands for E-selectin carry SLex-type glycans. The leukocyte β2 integrins are glycosylated with SLex. Thus, we speculated that β2 integrins could support attachment to E-selectin. To test this hypothesis, we coated 10–diameter microspheres with purified CD11b/CD18 (αMβ2) and investigated the adhesion of the resulting αMβ2 microspheres to E-selectin. Under in vitro flow conditions, the αMβ2 microspheres attached to Chinese hamster ovary cells expressing E-selectin (CHO-E) and 4-h interleukin-1 β-activated human umbilical vein endothelial cells (HUVEC). At a shear stress of 1.8 dynes/cm2, the attachment events were eliminated by pretreatment of the cellular monolayers with a mAb to E-selectin. microspheres did not attach to untransfected CHO cells or unactivated HUVEC at 1.8 dynes/cm2. Taken together, the results strongly suggest that the CD11b/CD18-E-selectin bond has sufficient biophysical properties to mediate attachment of neutro-phil-sized particles to E-selectin under flow. J. Leukoc. Biol. 67: 196–205; 2000.