bluuebunny/crossref_metadata_2025_split huggingface dataset:
Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules
Authors: Kjeldsen L , Calafat J , Borregaard N 
Published: January 2018

Abstract
The abnormal giant granules of Chediak-Higashi syndrome (CHS) neutrophils in humans are thought to be derived from both azurophil and specific granules, whereas the presence of gelatinase granules and their contribution to giant granule formation has not been investigated previously. We have examined the ultrastructure and mobilization of neutrophil granules from a patient with CHS by immunogold electron microscopy and exocytosis experiments of isolated leukocytes. The giant granules contained the azurophil granule components myeloperoxidase and CD63. We found no evidence of involvement of specific or gelatinase granules in the formation of giant granules because lactoferrin and gelatinase were contained in normal-appearing peroxidase-negative granules. On stimulation of leukocytes with N-formyl-methionyl-leucyl-phenylalanine and the calcium ionophore, ionomycin, there was a diminished exocytosis of myeloperoxidase in CHS compared with a healthy control, indicating a lack of mobilization of the giant granules. On the other hand, there was a normal or augmented release of lactoferrin and gelatinase in CHS neutrophils, with gelatinase granules being the most easily mobilized, as known from normal neutrophils. In conclusion, giant granules from CHS neutrophils originate from azurophil granules but not from the specific and gelatinase granules. J. Leukoc. Biol. 64: 72–77; 1998.
A soluble form of the urokinase plasminogen activator receptor (suPAR) can bind to hematopoietic cells
Authors: Mizukami Ikuko F , Todd Robert F 
Published: January 2018

Abstract
The receptor for urokinase plasminogen activator (uPAR; CD87) is a 50- to 65-kDa glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed by leukocytes and tumor cells where it facilitates uPA-dependent, plasmin-mediated pericellular proteolysis during cellular invasion. Because uPAR is inducibly shed into culture supernatants and human body fluids, we tested the hypothesis that soluble uPAR (suPAR) can bind to the plasma membrane of hematopoietic cells where it might modulate their invasive phenotype. As measured by flow cytometry, recombinant biotinylated-suPAR (B-suPAR) bound in a specific fashion to THP-1 leukemia cells and blood PMNs and monocytes (but not to lymphocytes). B-suPAR also demonstrated specific binding to a variety of leukemic lines, including cells that are positive or negative for membrane uPAR expression. Binding of B-suPAR to THP-1 cells was enhanced four- to sevenfold by 24-h exposure of cells to PMA or by coincubation with uPA ligand (but not its isolated catalytic and binding fragments). Conversely, binding of B-suPAR to PMNs was unaffected by brief exposure to fMLP, and was inhibited by coincubation with uPA. B-suPAR binding to PMA-differentiated THP-1 cells in the presence of uPA was further enhanced by acid washing (removing endogenous uPA) but was partially inhibited by treatment of cells with trypsin. Pretreatment of PMA-differentiated THP-1 cells and unstimulated PMNs with soluble sugars, calcium chelators, and antibodies specific for integrins or extracellular matrix proteins failed to consistently block the binding of B-suPAR. Whereas the binding of suPAR did not measurably affect cell-associated plasmin activation, suPAR did competitively inhibit the binding of exogenous uPA to membrane-associated uPAR. These observations support the hypothesis that suPAR can bind specifically to trypsin-sensitive receptors expressed by certain normal and neoplastic hematopoietic cells where its binding is variably influenced by uPA ligand. J. Leukoc. Biol. 64: 203–213; 1998.
Interleukin-18/interferon-γ-inducing factor, a novel cytokine, up-regulates ICAM-1 (CD54) expression in KG-1 cells
Authors: Kohka Hideo , Yoshino Tadashi , Iwagaki Hiromi , Sakuma Isao , Tanimoto Tadao , Matsuo Yosinobu , Kurimoto Masashi , Orita Kunzo , Akagi Tadaatsu , Tanaka Noriaki 
Published: January 2018

Abstract
Intercellular adhesion molecule-1 (ICAM-1, CD54) is a membrane glycoprotein and a member of the immunoglobulin superfamily. It plays a central role in cell to cell-mediated immune responses and is a ligand for leukocyte function-associated antigen-1 (LFA-1). We report here that a newly discovered cytokine, interferon-γ-inducing factor (IGIF) [H. Okamura et al. (1995) Nature 378, 88] recently proposed to be designated as IL-18, selectively up-regulates ICAM-1 expression in KG-1 cells, a human myelomonocytic cell line, in which IL-18 also enhances interferon-γ production. IL-18 induced heterotypic aggregation between KG-1 and Peer T cells, which was blocked by anti-ICAM-1 and/or LFA-1 antibodies. Anti-interferon-γ antibody did not block the IL-18-induced up-regulation of ICAM-1 on KG-1 cells. These results thus show that IGIF/IL-18, enhances ICAM-1 expression in KG-1 cells in an interferon-γ-independent pathway, up-regulates ICAM-1 functions, and that IL-18 might play a potential role in immunoregulation by mediating immune cell infiltration into the tissues. J. Leukoc. Biol. 64: 519–527; 1998.
The IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte lineage, but is rapidly and markedly down-regulated in other myeloid precursor populations
Authors: Dawson Michelle J , Elwood Ngaire J , Johnstone Ricky W , Trapani Joseph A 
Published: January 2018

Abstract
IFI 16 is an interferon-inducible nucleoprotein expressed by human monocytes. IFI 16 and a related mouse protein, p202, control cellular proliferation by binding and modulating the functions of cell cycle regulatory factors including p53 and the retinoblastoma gene product, pRb. In this study, we examined IFI 16 expression in myeloid precursor cells cultured in vitro in colony-forming assays using granulocyte (G-) and granulocyte-macrophage (GM-) colony-stimulating factor (CSF). IFI 16 was expressed in 100% of CD34+ cells isolated from human bone marrow. When the CD34+ cells were induced to differentiate, two subpopulations of cells were identified by two-color cytofluorography: the CD14+ (monocytoid) cells all expressed IFI 16, whereas the CD14– (polymorphonuclear precursor) cells did not. The strongest expression of IFI 16 was in the cells staining brightest for CD14, whereas depletion of CD14+ monocytoid cells from mixed monocytic/granulocytic cultures largely abolished IFI 16-stained cells. Furthermore, in eight independent colony-forming assays, the number of IFI 16+ cells correlated closely with the numbers of monocyte precursors identified morphologically (R2 = 0.99), but was unrelated to the numbers of myelocytes, promyelocytes, and metamyelocytes; nor was IFI 16 expressed by erythroid or eosinophil precursors. We conclude that IFI 16 is expressed in CD34+ and monocytoid daughter cells, but is rapidly and markedly down-regulated at the corresponding stages of polymorphonuclear and erythroid development. This differential expression of IFI 16 in myeloid precursor subpopulations and its perceived molecular properties are consistent with a possible role in regulating myelopoiesis. J. Leukoc. Biol. 64: 546–554; 1998.
Role of the mitogen-activated protein kinases and tyrosine kinases during leukotriene B4-induced eosinophil activation
Authors: Lindsay Mark A , Haddad El-Bdaoui , Rousell Jonathan , Teixeira Mauro M , Hellewell Paul G , Barnes Peter J , Giembycz Mark A 
Published: January 2018

Abstract
Exposure of guinea-pig eosinophils to leukotriene B4 (LTB4; 1 μM) resulted in a rapid generation of H2O2 (index of NADPH oxidase activation), stimulated [3H]arachidonic acid (AA) release (index of phospholipase A2 activity), and promoted CD18-dependent homotypic aggregation. Under similar conditions, LTB4 (1 μM) induced a rapid activation of extracellular-regulated kinases-1 and 2 (ERK-1/2) but not c-jun N-terminal kinases 46 and 54 (JNK-46/54) or p38 mitogen-activated protein kinase (p38 MAP kinase). To examine the role of ERK-1/2 in the mechanism of eosinophil activation, a selective inhibitor of MAP kinase kinase-1/2 (MEK-1/2), PD098059, was employed. However, PD 098059 at concentrations that attenuated ERK-1/2 activation had no significant affect on eosinophil activation. In contrast, a role for tyrosine kinases in LTB4-induced eosinophil activation was suggested by studies with the tyrosine kinase inhibitors, herbimycin A and lavendustin A. However, the results of those experiments implied divergent pathways for the control of eosinophil responses because the inhibitors were more effective at attenuating H2O2 generation than [3H]AA release, and had little effect on homotypic aggregation. J. Leukoc. Biol. 64: 555–562; 1998.
β2-Integrins mediate stable adhesion in collisional interactions between neutrophils and ICAM-1-expressing cells
Authors: Lynam Eric , Sklar Larry A , Taylor Andrew D , Neelamegham Sriram , Edwards Bruce S , Smith C Wayne , Simon Scott I 
Published: January 2018

Abstract
The aggregation of human neutrophils in suspension has features that are analogous to their attachment to activated endothelium in that both involve selectin and β2-integrin adhesion receptors. For the collisional interaction that forms neutrophil aggregates in suspension, there is a tethering step in which L-selectin on neutrophils binds PSGL-1. At relatively low shear rates (100–200 s-1) firm adhesion is mediated in equal measure by LFA-1 binding to ICAM-3, and Mac-1 binding to an as yet undefined ligand. In this report we used a mouse melanoma cell line expressing an estimated 700,000 ICAM-1 (CD54) to examine the relative roles of LFA-1 and Mac-1 over the kinetics of heterotypic cell adhesion in shear mixed suspensions. Neither heterotypic nor homotypic neutrophil aggregates formed with application of shear alone. However, the rate of aggregation peaked within seconds of chemotactic stimulation. In contrast to homotypic aggregation, neither L-selectin nor its O-glycoprotein ligands on neutrophils contributed to heterotypic adhesion. Adhesion was inhibited in a dose-dependent manner as ICAM-1 was titrated with blocking mAb. A direct interaction between LFA-1 and ICAM-1 was preferred over the first minute of stimulation, whereas at later times adhesion was supported equally by Mac-1. Activation with MnCl2 also favored participation of the constitutively expressed LFA-1. Application of defined shear in a cone and plate viscometer showed that adhesion to the ICAM-1 cells decreased from a maximum level to baseline as shear rate increased up to 400 s-1 in a manner typical of integrin adhesion alone. In contrast, homotypic aggregation supported by the transition from selectin to integrin binding exhibited an increase in efficiency up to 800 s-1. The pathophysiological significance of receptor site density and duration of contact in collisional interactions relevant to leukocyte recruitment compared to leukocyte-endothelial cell interactions on surfaces is discussed. J. Leukoc. Biol. 64: 622–630; 1998.
Macrophage/fibroblast coculture induces macrophage inflammatory protein-1α production mediated by intercellular adhesion molecule-1 and oxygen radicals
Authors: Steinhauser Matthew L , Kunkel Steven L , Hogaboam Cory M , Evanoff Holly , Strieter Robert M , Lukacs Nicholas W 
Published: January 2018

Abstract
This study examined the cell-to-cell interaction between fibroblasts and macrophages as a possible contributor to the chronic inflammatory state. In a coculture system, consisting of macrophages layered over confluent fibroblasts, there was a significant increase in macrophage inflammatory protein 1α (MIP-1α) compared with control cultures. ICAM-1 adhesion was identified as an important stimulus of MIP-1α production by using ICAM-1-specific monoclonal antibodies. Furthermore, fibroblasts from ICAM-1 knockout mice induced significantly less MIP-1α production from peritoneal macrophages when compared to control fibroblasts. In addition, it appeared that oxygen radicals functioned as activating molecules during cellular interaction and production of MIP-1α, as the addition of the antioxidant N-acetylcysteine (NAC) prevented MIP-1α secretion. Thus, the ICAM-1 and oxygen radical-mediated induction of MIP-1α associated with a macrophage/fibroblast coculture system provides one possible mechanism by which immune/inflammatory cell interactions may augment chemokine production and exacerbate chronic inflammatory diseases. J. Leukoc. Biol. 64: 636–641; 1998.
Glycosaminoglycan profile in macrophages exposed to Candida albicans and interleukins
Authors: Bodo Maria , Blasi Elisabetta , Becchetti Ennio , Giammarioli Monica , Conte Carmela , Bellocchio Silvia , Baroni Tiziano , Bellucci Catia , Bistoni Francesco 
Published: January 2018

Abstract
Glycosaminoglycans (GAG), are extracellular matrix macromolecules that affect the phagocytic properties of macrophages. In order to assess whether the interaction between macrophages and Candida albicans (iCa) provokes changes in the phenotype, we analyzed the GAG profiles in two macrophage lines, ANA-1 (from murine bone-marrow) and BV-2 (from murine brain). We also investigated GAG modulation by interleukin-1α (IL-1α) and interleukin-6 (IL-6). During iCa treatment and even after the addition of ILs, ANA-1 accumulated less total GAG compared to controls. IL-1 treatment, combined with iCa exposure, induced a decrease in heparan sulfate and chondroitin sulfate chains, and an increase in the hyaluronic acid percentage. IL-6 treatment, with or without iCa, decreased the hyaluronic acid/sulfated GAG ratio. The GAG pattern in BV-2 appears to be different to ANA-1 and iCa exposure does not induce any difference in total GAG. The inhibitory effect induced by ILs on GAG synthesis is less than that observed in ANA-1 and the GAG elution profile is modulated to a lesser extent by treatment with ILs and/or iCa compared to the ANA-1. We suggest that the observed changes in the expression of the individual GAG classes may be responsible for the macrophage functional heterogeneity. J. Leukoc. Biol. 64: 650–656; 1998.
Murine DEP-1, a receptor protein tyrosine phosphatase, is expressed in macrophages and is regulated by CSF-1 and LPS
Authors: Osborne Julie M , Elzen Nicole den , Lichanska Agnieszka M , Costelloe Elaine O , Yamada Toshiya , Cassady A Ian , Hume David A 
Published: January 2018

Abstract
The spectrum of protein tyrosine phosphatases (PTPs) expressed in bone marrow-derived murine macrophages (BMMs) was examined using reverse transcriptase-polymerase chain reaction. Ten different PTP cDNAs were isolated and in this study we focus on mDEP-1, a type III receptor PTP. Three mDEP-1 transcripts were expressed in primary macrophages and macrophage cell lines and were induced during macrophage differentiation of M1 myeloid leukemia cells. A variant mRNA was identified that encodes an alternate carboxyl-terminus and 3 UTR. The expression of mDEP-1 was down-regulated by CSF-1 (macrophage colony-stimulating factor) and up-regulated by bacterial lipopolysaccharide, an important physiological regulator of macrophage function that opposes CSF-1 action. Whole mount in situ hybridization, and immunolocalization of the protein, confirmed that mDEP-1 is expressed by a subset of embryonic macrophages in the liver and mesenchyme. mDEP-1 was also detected in the eye and peripheral nervous system of the developing embryo. Attempts to express mDEP-1 constitutively in the macrophage cell line RAW264 were unsuccessful, with results suggesting that the gene product inhibits cell proliferation. J. Leukoc. Biol. 64: 692–701; 1998.
Extrathymic T cell differentiation in vitro from human CD34+ stem cells
Authors: Pawelec Graham , Muller Robert , Rehbein Arnika , Hähnel Karin , Ziegler Benedikt L 
Published: January 2018

Abstract
Although it is well established that T cells are derived from CD34+ stem cells in vivo, and that T cells can develop in the absence of a functioning thymus, it has not proven possible thus far to generate human T cells in vitro from CD34+ cells in the absence of any thymic influence. We now present a limiting dilution cloning culture system that supports the differentiation of highly purified human CD34+ cells to CD3+ T cells in vitro in the complete absence of any thymic components. The culture system features the use of a serum-free medium supplemented with a cocktail of cytokines including flt-3 ligand, interleukin-3 (IL-3), stem cell factor (SCF), and IL-2. CD4+ T cell clones capable of mitogen-stimulated proliferation and response to IL-2, and expressing a varied TCR-Vβ repertoire were obtained under these conditions. This culture system therefore supports human T lymphopoiesis in the absence of any thymic influence and may prove useful for the evaluation of extrathymic T cell differentiation in vitro. J. Leukoc. Biol. 64: 733–739; 1998.
Thermal injury alters macrophage responses to prostaglandin E2: contribution to the enhancement of inducible nitric oxide synthase activity
Authors: Schwacha Martin G , Samy T S Anantha , Catania Robert A , Chaudry Irshad H 
Published: January 2018

Abstract
Prostaglandin E2 (PGE2) and macrophage (Mϕ) -derived reactive nitrogen intermediates (RNI) have been implicated in T cell dysfunction after thermal injury. Normally, Mϕ inducible nitric oxide synthase (iNOS) activity can be regulated by PGE2, however, it is unknown whether PGE2 modulates Mϕ iNOS activity after thermal injury. Splenic Mϕ isolated from mice 7 days after thermal injury produced higher levels of RNI than Mϕ from sham mice when stimulated with lipopolysaccharide (LPS) or interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) in combination. PGE2, when added concurrently with LPS, suppressed RNI production by Mϕ from sham mice, whereas Mϕ from injured mice were unaffected. When Mϕ were pretreated with PGE2 before LPS, RNI production was suppressed in both populations. RNI production in response to IFN-γ or IFN-γ and TNF-α in combination was enhanced by PGE2 in both populations, however, the effect was markedly greater in Mϕ from injured mice. The PGE2-mediated changes in RNI production were paralleled by similar changes in iNOS protein expression, suggesting that the effect of PGE2 was at the level of enzyme expression rather than activity. Dibutryl cAMP induced similar effects as PGE2, suggesting the response to PGE2 after thermal injury is independent of potential changes in PGE2-induced adenylate cyclase activity and is cAMP-mediated. The results indicate that Mϕ from burned mice display an altered sensitivity to PGE2, resulting in enhanced iNOS activity. Thus, PGE2, which is elevated after thermal injury and can directly suppress T cell function, may also contribute to immune dysfunction through the enhancement of Mϕ iNOS activity. J. Leukoc. Biol. 64: 740–746; 1998.
Nucleosomes inhibit phagocytosis of apoptotic thymocytes by peritoneal macrophages from MRL+/+ lupus-prone mice
Authors: Laderach Diego , Bach Jean-François , Koutouzov Sophie 
Published: January 2018

Abstract
The nucleosome, the basic structure of chromatin and normal product of cell apoptosis, plays a pivotal role both in the induction and the pathogenesis of systemic lupus erythematosus (SLE). Nucleosomes have been found to circulate at high levels in patients with SLE and apoptosis of lymphoid cells is increased during human and murine lupus. In this study, we examined the presence of possible defects in clearance mechanisms of apoptotic cells in murine lupus, and questioned further whether nucleosomes could compromise this phagocytic process. There did not appear to be any intrinsic functional defect of macrophages from young MRL+/+ lupus-prone mice to recognize and phagocytose apoptotic thymocytes. Nucleosomes, as a mimic of increased cell apoptotsis in vivo, induced a strong, dose-dependent, inhibition of phagocytosis of apoptotic thymocytes by young, pre-autoimmune, macrophages of MRL+/+ mice, whereas macrophages of non-autoimmune C3H mice only exhibited a trend to inhibition. The nucleosome-elicited inhibitory effect persisted during the development of the autoimmune response and appeared to be specific for the molecular mechanisms involved in macrophage phagocytosis of apoptotic cells. Our data suggest that nucleosome elicited inhibition of phagocytosis of apoptotic cells by MRL+/+ macrophages before the onset of the autoimmune response contribute, in a positive loop, to sustain and/or augment the levels of circulating (and potentially immunogenic) nucleosomes in lupus. J. Leukoc. Biol. 64: 774–780; 1998.
CD43 is associated with tyrosine kinase activity in human neutrophils
Authors: Skubitz Keith M , Campbell Kenneth D , Skubitz Amy P N 
Published: January 2018

Abstract
CD43 appears to be involved in signal transduction, however, the mechanism of this function is unknown. Protein kinase activity was detected in neutrophils associated with CD43. Most of the protein kinase activity associated with these antigens was tyrosine kinase activity. The src family kinases lyn and hck were found to account for much of the associated tyrosine kinase activity. The data suggest that associated tyrosine kinase activity may play a role in signal transduction via CD43 to regulate other cell functions. J. Leukoc. Biol. 64: 800–802; 1998.
CSF-1 regulation of I6 gene expression by murine macrophages: a pivotal role for GM-CSF
Authors: Evans Robert , Shultz Leonard D , Dranoff Glen , Fuller Jane A , Kamdar Sonya J 
Published: January 2018

Abstract
We test the hypothesis that the monocyte-macrophage colony-stimulating factor (CSF-1 or M-CSF) plays a major role in the inflammatory responses of Mϕ by acting as a priming agent that heightens their responsiveness to secondary stimulation by other mediators. We previously reported that CSF-1 induced peritoneal Mϕ (PMϕ) to transcribe several genes including interleukin-6 (I6) and granulocyte-macrophage colony-stimulating factor (Csfgm). It was reported that the I6 and Csfgm genes were individually regulated by different pathways but it was not clear to what extent the two genes interacted during Mϕ-mediated inflammatory responses. We now show that CSF-1 induces the release of bioactive GM-CSF from mouse resident PMϕ. GM-CSF induces I6 gene expression and synergizes with CSF-1 to induce the release of large amounts of IL-6. PMϕ from C57BL/6J-Csfgmnull mice were shown to release minimal IL-6 in response to CSF-1 and to express a much reduced response to the highly stimulatory combination of CSF-1 and lipopolysaccharide (LPS). Exogenous recombinant GM-CSF restored the IL-6 response of GM-CSF null PMϕ to a great extent but not completely. As controls, three other recombinant proteins were tested but of these only tumor necrosis factor α (TNF-α) was shown to synergize with both CSF-1 and GM-CSF. Using PMϕ from mice deficient in the expression of the I6 gene, it was shown that they released two- to threefold more GM-CSF in response to CSF-1 than their control counterparts. However, an exogenous supply of recombinant IL-6 had no effect on GM-CSF release. The data indicate that the pathways regulating I6 gene expression are under the control of a complex network of cytokine interactions involving at least CSF-1, GM-CSF, and TNF-ϕ, with the added possibility that IL-6 may exert modulatory activity within this network. J. Leukoc. Biol. 64: 810–816; 1998.