bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of nitric oxide in the regulation of peripheral blood leukocyte counts
Authors: Geffner Jorge R , Trevani Analía S , de D’Elia Isabel , Diament Miriam , Klein Danka , Giordano Mirta 
Published: January 2018

Abstract
A role for nitric oxide (NO) in the regulation of blood leukocyte numbers was examined in BALB/c mice by employing the NO synthase inhibitor NG-nitro L-arginine methyl ester (L-NAME). Treatment of animals with a single dose of 50 mg/kg body wt caused a dramatic increase in the number of circulating neutrophils and a moderate decrease in the number of circulating lymphocytes. These effects were partially reversed by the simultaneous inoculation of L-arginine (250 mg/kg body wt.) but not by D-arginine. A second NO synthase inhibitor, NG-nitro L-arginine, induced changes comparable to those elicited by L-NAME. Because catecholamines and glucocorticoids are well-known modulators of blood leukocyte counts, experiments were carried out in adrenalectomized mice. It was found that adrenalectomy did not modify the increase in the number of circulating neutrophils induced by L-NAME but completely prevented the decrease of circulating lymphocytes. Taken together, these findings support the hypothesis that NO plays an important role in the regulation of the peripheral blood number of neutrophils and lymphocytes, and that this function involves, in each case, the participation of different mechanisms.
Expression of leukocyte differentiation antigens during the differentiation of HL-60 cells induced by 1,25-dihydroxyvitamin D3: comparison with the maturation of normal monocytic and granulocytic bone marrow cells
Authors: Brackman Damien , Lund-Johansen Fridtjof , Aarskog Dagfinn 
Published: January 2018

Abstract
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces monocytic differentiation of the HL-60 leukemic cell line. The present study investigated whether and to what extent this differentiation resembles the normal maturation of monocytic cells in the bone marrow. Multidimensional flow cytometry was used to identify changes in antigen expression that occur in normal bone marrow cells at distinct stages of monocytic and granulocytic maturation. HL-60 cells were analyzed in the same manner after exposure to 1,25-(OH)2D3 to determine whether the hormone induces a similar sequence of phenotypic changes. In the leukemic cells, monocytic features were sequentially induced and several maturational steps could be resolved. CD14, CD32, CD53, CD15, CDw65, CD29, CD16, and CD66b were modulated in 1,25-(OH)2D3-induced HL-60 cells as in the normal monocytic maturational pathway. Differences were observed for CD15s and CDw17. The expression pattern of CD44 during differentiation of HL-60 cells resembled that in granulocytic cells. The results therefore suggest that 1,25-(OH)2D3 induces a differentiation program in HL-60 cells that in many ways resembles that of normal monocytic cells in the bone marrow but also carries elements of the granulocytic pathway.
Autocrine regulation of collagenase gene expression by TNF-α in U937 cells
Authors: Callaghan Máire M , Lovis Rosa M , Rammohan Chidambaram , Lu Yang , Pope Richard M 
Published: January 2018

Abstract
Tumor necrosis factor α (TNF-α) has been shown to induce the production of interstitial collagenase by fibroblasts and chondrocytes. We investigated the role of TNF-α in collagenase gene expression by U937 monocyte/macrophage cells. Transcription of the TNF-α gene was observed after 0.5 h of phorbol myristate acetate (PMA) stimulation. Collagenase mRNA expression was not observed until 5–7 h of activation with PMA. TNF-α was detected in the culture supernatants 2–3 h before transcription of the collagenase gene. Neutralization of TNF-α protein with anti-TNF-α antibodies significantly reduced collagenase mRNA expression. Protein kinase C (PKC) and protein tyrosine kinase (PTK) inhibition essentially abolished both PMA-induced TNF-α protein secretion and collagenase mRNA expression. Collagenase gene expression induced by exogenous TNF-α in U937 cells stimulated with a suboptimal concentration of PMA was sup-pressed by PTK, but not PKC, inhibition. The pyrrolidine derivative of dithiocarbamate, a potent inhibitor of nuclear factor-κB (NF-κB) activation, resulted in a marked reduction in collagenase gene transcription, however, no reduction of TNF-α secretion was noted. Anti-TNF-α antibodies inhibited PMA-induced NF-κB activation. These observations demonstrate an important role for TNF-α in the autocrine regulation of collagenase gene expression by U937 cells. Additionally, TNF-α-induced PTK and NF-κB activation were important in collagenase gene expression in this cell line.
Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1
Authors: Proost Paul , Wuyts Anja , van Damme Jo 
Published: January 2018

Abstract
Structurally, the monocyte chemotactic proteins MCP-1, -2, and -3 form a subfamily of the C-C or β-chemokines. Like other chemokines, MCPs are produced by a variety of cells on stimulation with cytokines (interleukin-1, tumor necrosis factor-α, interferon-γ), bacterial and viral products or mitogens. MCP-1 levels are enhanced during infection and inflammation, which are characterized by leukocyte infiltration. In vitro, MCPs are chemotactic for a distinct spectrum of target cells and show different specific biological activities depending on the cell type and the chemokine tested. MCP-3 has the broadest range in that it activates monocytes, dendritic cells, lymphocytes, natural killer cells, eosinophils, basophils, and neutrophils. The most sensitive cells to all three MCPs are lymphocytes and monocytes. MCP-1 is a potent basophil activator but does not attract eosinophils, whereas, at higher concentrations, MCP-2 also stimulates both eosinophils and basophils. The signal transduction of MCPs on monocytes involves at least two G protein-linked C-C chemokine receptors: C-C CKR-1 binds MCP-3 and C-C CKR-2 binds MCP-1 and MCP-3 but not MCP-2. Receptor binding leads to enhanced [Ca2+]i for all chemokines except for MCP-2.
Novel insight into molecular mechanism of endotoxin shock: biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-κB and regulation of cytokine production/action through β2 integrin in vivo
Authors: Mukaida Naofumi , Ishikawa Yuji , Lkeda Naoki , Fujioka Nakaba , Watanabe Shun-ichi , Kuno Kouji , Matsushima Kouji 
Published: January 2018

Abstract
Lipopolysaccharide (LPS), a constituent of gram-negative bacteria cell wall, plays an essential role in the pathogenesis of septic shock by generating endogenous mediators such as cytokines, nitrous oxide, superoxide anions, and lipid mediators. In vitro, LPS induces the transcription of a set of genes involved in inflammatory reactions by activating several types of transcription factors, particularly nuclear factor-κB (NF-κB). An analysis of NF-κB activation using a cell-free system demonstrated that two pathways converge to activate NF-κB; one is staurosporine-sensitive, the other is staurosporine-insensitive and tyrosine kinase-dependent. Furthermore, the latter pathway culminates in IκBaL phosphorylation at serine/threonine residues in its carboxyl-terminal acidic region with dissociation of IκBα from NF-κB, thereby activating NF-κB. The requirement for the phosphorylation at this site was confirmed by the specific inhibition of NF-κB activation in a cell-free system by the synthetic peptide corresponding to this site. The in vivo administration of an anti-CD18 antibody prevented elevation of plasma tumor necrosis factor (TNF) levels and acute lethality induced by injection of a low dose of LPS into Propionibacterium acnes-primed rabbits or by the administration of a single high dose of LPS into animals. Anti-CD18 also prevented acute lethality induced by one of the main mediators of endotoxin shock, TNF-α. Furthermore, an antibody to a ligand for CD18, intercellular adhesion molecule-1, also prevented TNF-induced shock as well as endotoxin shock in rabbits. These observations suggest that the interaction between leukoytes and endothelium through β2. integrin adhesion molecules may be of primary importance in mediating LPS signals in vivo.
Role of CSBP/p38/RK stress response kinase in LPS and cytokine signaling mechanisms
Authors: Lee John C , Young Peter R 
Published: January 2018

Abstract
A new member of the mitogen-activated protein kinase family, alternatively termed CSBP, p38, or RK, has been identified independently by several laboratories recently. Activation of this novel protein kinase via dual phosphorylation has been observed in different cell systems upon stimulation by a wide spectrum of stimuli, such as physicochemical stress and treatment with lipopolysaccharide or proinflammatory cytokines such as interleukin-1 and tumor necrosis factor. Furthermore, CSAID™ cytokine biosynthesis inhibitors have now been determined to be potent and selective inhibitors of CSBP/p38/RK kinase activity. These inhibitors will help to dissect signaling pathways involved in inflammatory responses. In particular, for the first time a definitive signal transduction pathway can be prescribed to the action of lipopolysaccharide in cytokine production in macrophages.
Silicotic lymph node reactions in mice: genetic differences, correlation with macrophage markers, and independence from T lymphocytes
Authors: Weirich Uta , Friemann Johannes , Rehn Bernd , Henkelüdecke Uwe , Lammers Thorsten , Sorg Clemens , Bruch Joachim , Gleichmann Ernst 
Published: January 2018

Abstract
Quartz was injected into a hind foot of BALB/c and DBA/2 mice and on days 40, 90, and 180 the progressive response ensuing in the draining popliteal lymph node (PLN) was investigated by histopathology and immunohistopathology. The area of silicotic nodules (ASN) was measured by morphometry, and, by this parameter, strain BALB/c proved to be a high responder to quartz, and strain DBA/2 a low responder, albeit both strains showed a similar degree of reactive lymphoid hyperplasia in the draining PLN. Both strains also showed a similar quartz content in the draining PLN but in BALB/c mice quartz particles were concentrated in the ASN, whereas in DBA/2 mice they were evenly dispersed over the PLN. Because the silicotic response of athymic BALB/c nu/nu mice was even stronger than that of euthymic BALB/c mice, T cells are not required for the development of silicotic nodules. This fits the notion that quartz is not an antigen and that high and low responder strains are MHC-identical. Because quartz-treated BALB/c, but not DBA/2 mice, showed a persistent expression of the macrophage differentiation markers MRP8 and MRP14, phenotypically the observed strain difference in silicotic responsiveness seems to be expressed at the level of macrophages.
α-MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line
Authors: Rajora N , Ceriani G , Catania A , Star R A , Murphy M T , Lipton J M 
Published: January 2018

Abstract
α-Melanocyte-stimulating hormone (α-MSH), a tridecapeptide derived from pro-opiomelanocortin, has potent antiinflammatory activity in laboratory animals. α-MSH inhibits nitric oxide production by murine macrophages, an influence believed to reflect activation of an autocrine circuit in these cells, one that is based on production and release of α-MSH and subsequent stimulation of melanocortin receptors. We found that THP-1 cells, human monocytic cells, produced α-MSH; this production was increased by interleukin-6, tumor necrosis factor α, or concanavalin A. These cells also expressed the gene for the human α-MSH receptor MC1. Unlike murine macrophages, THP-1 cells produced little nitrite in response to interferon-γ(IFN-γ) and lipopolysaccharide, and a-MSH inhibited this production only slightly. However, production of neopterin, a presumed primate homologue of nitric oxide in lower animals, was increased in THP-1 cells stimulated with IFN-γ plus TNF-α and α-MSH significantly inhibited this production. The evidence indicates that an autocrine regulatory circuit based on α-MSH occurs in human monocyte/macrophages much as in murine macrophages. α-MSH-induced modulation of specific inflammatory mediators/cytotoxic agents appears to differ depending on the importance of the mediators in the myelomonocytic cells of different species.
Mechanisms involved in eosinophil migration. Platelet-activating factor-induced Chemotaxis and interleukin-5-induced chemokinesis are mediated by different signals
Authors: Schweizer René C , van Kessel-Welmers Berns A C , Warringa Ruud A J , Maikoe Tjander , Raaijmakers Jan A M , Lammers Jan-Willem J , Koenderman Leo 
Published: January 2018

Abstract
Eosinophils play an important role in the pathogenesis of allergic diseases such as allergic asthma. Eosinophil migration in vitro can be divided into directed migration, or Chemotaxis, and random migration, or chemokinesis. Here, we studied intracellular signals involved in eosinophil migration in vitro induced by platelet-activating factor (PAF) and interleukin-5 (IL-5), applying a Boyden chamber assay. Migration induced by PAF (10-11-10-6 M) largely consisted of Chemotaxis with some chemokinesis, whereas IL-5 (10-12-10-8 M) induced chemokinesis only. Eosinophils were depleted from intracellular and extracellular Ca2+ to study the role of Ca2+ as a second messenger. Ca2+ depletion did not change PAF-induced Chemotaxis, however, IL-5-induced chemokinesis was inhibited. Interestingly, PAF, but not IL-5, induced changes in [Ca2+]i. This rise originated mainly from internal stores. Inhibition of protein kinase A by H-89 and protein kinase C by GF 109203X had no effect on both forms of eosinophil migration. Addition of the protein kinase inhibitor staurosporine significantly inhibited IL-5-induced chemokinesis. Inhibition of tyrosine kinases by herbimycin A completely blocked IL-5-induced chemokinesis. PAF and IL-5-induced actin polymerization was studied to compare migratory responses with a migration-associated intracellular response. Ca2+ depletion significantly enhanced PAF-induced (10-8 M) actin polymerization, whereas IL-5-induced actin polymerization was not influenced. Addition of staurosporine led to an increase in F-actin. Subsequent addition of PAF or IL-5 resulted in an additive increase in F-actin content. In summary, both forms of eosinophil migration are protein kinase A and protein kinase C independent. In contrast to PAF-induced Chemotaxis, IL-5-induced chemokinesis was found to be completely Ca2+ and tyrosine kinase dependent.
Gene transfer for cytokine functional studies in the lung: the multifunctional role of GM-CSF in pulmonary inflammation
Authors: Xing Zhou , Braciak Todd , Ohkawar Yuichi , Sallenave Jean-Michel , Foley Ronan , Sime Patricia J , Jordana Manel , Graham Frank L , Gauldie Jack 
Published: January 2018

Abstract
Using adenoviral-mediated gene transfer techniques, the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene is efficiently targeted to and highly expressed by the respiratory epithelium of rat lung. This lung tissue-directed expression of GM-CSF induces accumulation of both eosinophils and macrophages at early stages and an irreversible fibrotic reaction at later stages. These tissue responses to GM-CSF appear to be distinct from those induced by other proinflammatory cytokines, interleukin (IL) -5, IL-6, macrophage inflammatory protein-2 (MIP-2), or RANTES overexpressed in the lung. These findings clearly demonstrate that GM-CSF is more than a hematopoietic cytokine in the lung and may play a pivotal role in the multiple pathological processes underlying numerous respiratory illnesses, including asthma. In this overview, the differences in tissue responses induced by GM-CSF and other individual cytokines are highlighted. In addition, the mechanisms by which GM-CSF contributes to the development of eosinophilia, macrophage granuloma, and fibrosis are discussed in conjunction with the recent findings from us and others.
Serglycin-binding proteins in activated macrophages and platelets
Authors: Kolset Svein O , Mann David M , Uhlin-Hansen Lars , Winberg Jan-Olof , Ruoslahti Erkki 
Published: January 2018

Abstract
The major proteoglycan in macrophages and platelets is the chondroitin sulfate proteoglycan serglycin. To study the biological role of serglycin, its binding to secreted and cell-associated proteins from macrophages and blood platelets was examined. Affinity chromatography with serglycin-Sepharose and chondroitin sulfate-Sepharose was used to isolate proteoglycan-binding proteins from macrophages and platelets. Antibodies against human macrophage inflammatory protein-1α (MIP-1α) precipitated a 14-kDa 35S-methionine-labeled protein among the chondroitin sulfate binding proteins secreted from the macrophage-like U937 cells after stimulation. Two proteins from murine macrophage J774 cells with molecular masses of ~10 and 14 kDa were precipitated by an antiserum against the murine MIP-1α. Protein sequencing of fragments obtained by trypsin digestion of a 14-kDa chondroitin sulfate-binding protein from cell extracts of stimulated U937 cells revealed 100% homology with lysozyme, a bacteriolytic enzyme. Fragment of one other protein with approximate molecular mass of 8 kDa showed high homology with bone morphogenetic protein. Inhibition studies showed that chondroitin 6-sulfate inhibited the bacteriolytic activity of lysozyme in a competitive manner more efficiently than heparin and chondroitin 4-sulfate. Amino-terminal sequencing of two proteins from platelet extracts that bound to serglycin-Sepharose revealed that they corresponded to multimeric forms of human platelet factor 4 (PF4). Chondroitin sulfate-Sepharose was shown to be equally efficient in retaining PF4 from platelet extracts as serglycin-Sepharose, indicating that the glycosaminoglycan chains mediate the binding to PF4 in the intact proteoglycan molecule. Competition experiments showed that serglycin was as efficient as heparan sulfate in blocking the binding of [3H]chondroitin sulfate to PF4, whereas heparin was one order of magnitude more efficient. Affinity measurements using fluoresceinamine-labeled glycosaminoglycans showed that the affinity of heparin for PF4 is on the order of 30 nM, whereas chondroitin sulfate has an affinity of 260 nM. Both PF4, MIP-1α, and lysozyme play important roles in different types of inflammatory reactions. The interaction with serglycin may indicate that this proteoglycan is involved in the regulation of the inflammatory response.
Differences in the state of differentiation of THP-1 cells induced by phorbol ester and 1,25-dihydroxyvitamin D3
Authors: Schwende Heike , Fitzke Edith , Ambs Petra , Dieter Peter 
Published: January 2018

Abstract
Human THP-1 leukemia cells differentiate along the monocytic lineage following exposure to phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D3 (VD3). In the monocytic cell line THP-1, PMA treatment resulted in a more differentiated phenotype than VD3, according to adherence, loss of proliferation, phagocytosis of latex beads, and expression of GD11b and CD14. Both differentiating substances induced similar effects in the release of superoxide anions (O2-). VD3-differentiated cells did not release prostaglandin E2 (PGE2), in contrast to PMA-differentiated cells, and in PMA-differentiated cells phospholipase A2 (PLA2) activity and expression was increased. Lipopolysaccharide (LPS)-stimulated tumor necrosis factor-α (TNF-α) release was higher in PMA-treated cells. PMA- but not VD3-differentiation resulted in a translocation of protein kinase C (PKC) isoenzymes to membrane fractions. Both differentiating agents up-regulated the expression of PKC isoenzymes. Whereas VD3 elevated mainly the expression of PKC-β, PMA caused a strong increase in PKC-δ and a weak increase in PKC-α, PKC-, and PKC- expression. These results indicate that phorbol ester and the active metabolite of vitamin D induce different signal pathways, which might result in different achievement of differentiation.
Interleukin-6 stimulates neutrophil production of platelet-activating factor
Authors: Biffl Walter L , Moore Ernest E , Moore Frederick A , Barnett Carlton C , Silliman Christopher C , Peterson Verlyn M 
Published: January 2018

Abstract
Interleukin-6 (IL-6) is an integral mediator of the acute phase response to injury and infection; an exaggerated IL-6 response has been associated with adverse clinical events. The precise role of IL-6 is unclear, but it appears capable of modulating the functional repertoire of mature neutrophils (PMNs). Our previous work demonstrated that IL-6-stimulated PMNs are primed by lower concentrations of platelet-activating factor (PAF) than nonstimulated PMNs. Recently, we have found that IL-6 suppresses PMN apoptosis via a PAF-like mechanism. We hypothesized that IL-6 stimulates PMNs to produce PAF. PMNs isolated from healthy human donors were incubated with IL-6 (0.1–100 ng/ml) at 37°. Lipid production was measured by use of thin-layer chromatography, and PAF quantitated with a scintillation proximity assay. IL-6 (1 and 10 ng/ml) stimulated PMNs to produce increased quantities of PAF. PAF production was associated with an increase in PMN cytosolic calcium. These data may provide mechanistic insight into IL-6 regulation of PMN-mediated cytotoxicity and the role of PAF in mediating IL-6 effects on PMNs.
In vivo labeling of neutrophils using a fluorescent cell linker
Authors: Albertine Kurt H , Gee Mariys H 
Published: January 2018

Abstract
To study neutrophil circulation time and trafficking in vivo requires labeling the cells so that their movement can be followed temporally and spatially. Labeling procedures used to date, however, have relied on ex vivo separation and labeling methods, an undesired consequence of which may be neutrophil activation. Moreover, the labeled cells preferentially stick in the pulmonary circulation for several hours upon reinjection into the host. Therefore, we devised an alternate labeling procedure that relied on intra-arterial infusion of the fluorescent phagocytic cell linker PKH26. We infused PKH26 (5.5 × 10-6 M for 1 h) into six awake sheep and measured systemic and pulmonary hemodynamics and lung lymph dynamics continuously for 3–4 h after the infusion. We collected simultaneous arterial and venous blood samples hourly for 4 h, and again 24 h after the infusion ended, for white blood cell and neutrophil differential counts and to identify labeled cells in fresh smears by fluorescence and differential interference contrast (DIC) microscopy. Infusion of PKH26 had minimal and transient physiologic effects on systemic and pulmonary artery pressure, lung lymph flow, and leukocyte counts. Labeled cells were present in venous blood after the infusion for at least 24 h. DIC microscopy observation of the blood smears indicated that the fluorescently labeled cells were exclusively neutrophils. Unstimulated superoxide anion release from neutrophils isolated 2 and 24 h after PKH26 infusion was not different from baseline release. Phorbol myristate acetate-stimulated release was not affected either. The labeled neutrophils responded to chemoattractants by migrating to extravascular sites. Our results indicate that neutrophils can be selectively labeled in vivo, after which trafficking of the labeled neutrophils can be determined.