bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem cell factor
Authors: McNiece Ian K , Briddell Robert A 
Published: January 2018

Abstract
Stem cell factor (SCF) is the ligand for the tyrosine kinase receptor okit, which is expressed on both primitive and mature hematopoietic progenitor cells. In vitro, SCF synergizes with other growth factors, such as granulocyte colony-stimulating factor (G–CSF), granulocyte macrophage–colony-stimulating factor, and interleukin-3 to stimulate the proliferation and differentiation of cells of the lymphoid, myeloid, erythroid, and megakaryocytic lineages. In vivo, SCF also synergizes with other growth factors and has been shown to enhance the mobilization of peripheral blood progenitor cells in combination with G–CSF. In phase I/II clinical studies administration of the combination of SCF and G-CSF resulted in a two- to threefold increase in cells that express the CD34 antigen compared with G–CSF alone. Other potential clinical uses include ex vivo expansion protocols and in vitro culture for gene therapy. J. Leukoc. Biol. 58: 14–22; 1995.
Monomeric bovine IgG2 is a potent stimulus for bovine neutrophils
Authors: Tao Weng , Corbett Martin J , Pickett Walter 
Published: January 2018

Abstract
Bovine plasma contains factors that can stimulate bovine neutrophils. Bovine plasma at 1:1,000,000–1:1,000 dilution induced a dose-dependent superoxide production in bovine neutrophils. When bovine plasma was fractionated with a protein G column, only the IgG fraction contained induction activity. At similar concentrations purified IgG induced a much stronger response than that of plasma IgG. Purified monomeric bovine IgG induced a dose-dependent increase in superoxide production. The maximum induction can be achieved at 100 μg/ml of bovine IgG. When subclasses of bovine IgG were examined, monomeric bovine IgG2 potently stimulated bovine polymorphonuclear leukocytes. In contrast, bovine IgG1 failed to induce a response at similar concentrations, and neither bovine IgG F(ab’)2 and Fc were effective. Both recombinant bovine granulocyte-macrophage colony-stimulating factor (r-BoGM-CSF) and recombinant bovine granulocyte colony-stimulating factor (r-BoG-CSF) primed bovine neutrophils for superoxide production induced by bovine IgG. The above results suggest that: (1) bovine plasma contain factors that can activate bovine neutrophils; (2) bovine plasma IgG is the major component that is responsible for bovine neutrophil activation; (3) bovine plasma contains factors that can inhibit the effect of bovine IgG; (4) monomeric bovine IgG2, but not IgG1, can activate bovine neutrophils directly without Fc receptor cross-linkage; (5) the integrity of bovine IgG is important in bovine polymorphonuclear leukocyte activation; and (6) bovine neutrophil activation induced by bovine IgG can be primed by r-BoGM-CSF or r-BoG-CSF. J. Leukoc. Biol. 58: 203–208; 1995.
Effect of PGE2 and of agents that raise cAMP levels on macrophage activation induced by IFN-γ and TNF-α
Authors: Mauël Jacques , Ransijn Adriana , Corradin Sally Betz , Buchmüller-Rouiller Yolande 
Published: January 2018

Abstract
The effect of prostaglandin (PG) E2 on macrophage activation by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) was evaluated. Murine macrophages infected with Leishmania enriettii or Leishr mania major were activated by exposure to IFN-γ (10–50 U/ml) and TNF-α (30–3000 U/ml), leading to intracellular parasite destruction within 24–48 h. Leishmanicidal activity was markedly increased when activation was performed in the presence of PGE2 (10-9-10-7 M) or arachidonate (10-5 M, a PG precursor), concomitant with enhanced nitrite release and glucose oxidation through the hexose monophosphate shunt pathway. Conversely, activation was reduced by indomethacin and hydrocortisone, two inhibitors of PG synthesis. Parasite killing and nitrite production were fully restored by exogenous PGE2, indicating that inhibition by these drugs was related to their ability to block PG production. PG can stimulate adenylate cyclase, thus raising intracellular cAMP levels. Accordingly, dibutyryl-cAMP, theophylline (which prevents cAMP breakdown), and forskolin (an activator of adenylate cyclase) all stimulated macrophage activation. Finally, PGE2 and cAMP enhanced expression of inducible nitric oxide synthase mRNA in response to IFN-γ and TNF-α, and this effect was inhibited by the cAMP antagonist 2′-O-methyl adenosine. These findings are consistent with the hypothesis that PGE2 acts as a positive agonist in macrophage activation by IFN-γ and TNF-α via its capacity to modulate intracellular cAMP levels. .J Leukoc. Biol 58: 217–224; 1995.
Regulation of NK cells through the 80-kDa TNFR (CD120b)
Authors: Mason Anna T , McVicar Daniel W , Smith Craig A , Young Howard A , Ware Carl F , Ortaldo John R 
Published: January 2018

Abstract
By using monoclonal antibody specific for tumor necrosis factor receptor80 (TNFR80) (CD120b) and TNFRβo (CD 120a), we determined which receptor transduces the signals involved in activating natural killer (NK) cells. Purified CD56+CD3- large lymphocytes express TNFR80 but not TNFR60 and interleukin-2 (IL-2) up-regulates TNFR80 expression, consistent with NK cells being activated in vivo. Treatment of NK cells with anti-TNFR80 for 18 h enhanced the NK activity detected on K562 target cells mimicking the effect of TNF. In combination with IL-2, TNF enhanced the development of lymphokine-activated killing. However, only anti-TNFR80 abrogated IL-2 induction of lymphokine-activated killer cell activity. The activity of TNF or anti-TNFR80 was selective for NK cytotoxic function because they did not directly mimic IL-2 activation or induce significant proliferation, expression of cell surface activation antigens (CD25 or HLA-DR), or interferon-γ secretion. These results indicate that TNFR80 is an important signal transducing receptor for the differentiation of NK cells induced by TNF and IL-2. J. Leukoc. Biol. 58: 249–255; 1995.
A novel biological effect of platelet factor 4 (PF4): enhancement of LPS-induced tissue factor activity in monocytes
Authors: Engstad Charlotte Sissener , Lia Karin , Rekdal Øystein , Olsen Jan Ole , Østeoid Bjarne 
Published: January 2018

Abstract
In a previous study we have shown that granulocytes enhance lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes in a platelet-dependent reaction. The present investigation was undertaken to examine the role of a platelet activation product, platelet factor 4 (PF4), in LPS-induced TF activity in monocytes. Platelet lysate supernatant, purified PF4, and the COOH-terminal tridecapeptide of PF4, termed PF4(58–70), enhanced LPS-induced TF activity in monocytes of whole blood dose dependently. A monoclonal antibody against P-selectin eliminated the enhancing effect of PF4(58–70) on LPS-induced TF activity in monocytes, and PF4(58–70) was shown to act synergistically with tumor necrosis factor α (TNF-α). However, PF4(58–70) did not enhance TNF-α secretion in LPS-stimulated whole blood. The major effect of PF4(58–70) was granulocyte dependent. Our results suggest that PF4 might play an important role in LPS-stimulated monocyte TF activity of whole blood.
Stability of nuclear segments in human neutrophils and evidence against a role for microfilaments or microtubules in their genesis during differentiation of HL60 myelocytes
Authors: Campbell Michael S , Lovell Mark A , Gorbsky Gary J 
Published: January 2018

Abstract
The nucleus of the mature human neutrophil is segmented into three to five interconnected lobes. The physiological purpose of this segmentation is unknown, as is the mechanism by which the lobes are formed during differentiation. Using video observation of migrating human neutrophils simultaneously illuminated for fluorescence and phase-contrast microscopy, we analyzed nuclear movements with respect to cell shape changes. The number of nuclear lobes and their relative size remained constant during observation (up to 1 h). The thin connecting segments between the lobes elongated and attenuated extensively but never separated. Electron microscopic analysis of neutrophil nuclei revealed no specialized nuclear or cytoplasmic structures in the vicinity of connecting segments. With fluorescence in situ hybridization of whole chromosome probes, we determined that chromosomes are randomly distributed among neutrophil nuclear lobes. HL60 cells are a human myelocytic line that, with retinoic acid treatment, segment their nuclei and differentiate into neutrophil-like cells over several days. Using a rapidly responding variant line termed HL60/S4 (Cancer Res. 52, 949–954), we found that segmentation could be induced within 24 h. We tested the role of cytoskeletal elements in the process of nuclear segmentation. Neither the microtubule inhibitor nocodazole nor the microfilament inhibitor cytochalasin D prevented nuclear segmentation. Together, our studies suggest that nuclear lobes in neutrophils are relatively stable structures that are not generated by microtubule- or microfilament-dependent forces.
Cross-linking of CD18 primes human neutrophils for activation of the respiratory burst in response to specific stimuli: Implications for adhesion-dependent physiological responses in neutrophils
Authors: Liles W Conrad , Ledbetter Jeffrey A , Waltersdorph Ann W , Klebanoff Seymour J 
Published: January 2018

Abstract
Adhesion is known to prime neutrophils for physiological activation in response to cytokines and other stimuli. We have employed the technique of receptor cross-linking to study the potential role of CD18, the common β-subunit of the β2-integrin family of adhesion molecules, in the regulation of the respiratory burst, as measured by luminol-enhanced chemiluminescence and iodination, in human neutrophils. CD18 cross-linking primed neutrophils to activate the respiratory burst after stimulation with tumor necrosis factor α (TNF-α) (100 units/mL), formyl-methionyl-leucyl-phenylalanine (fMLP) (1 μM), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (1 μg/mL), but not granulocyte colony-stimulating factor (G-CSF) (1 μg/mL), interferon-γ (IFN-γ) (100 U/mL), or phorbol myristate acetate (100 nM). The maximal rate of chemiluminescence induced by fMLP, TNF-α, and GM-CSF was enhanced 8-, 6-, and 1.5-fold, respectively, following CD18 cross-linking. Priming of the respiratory burst by direct engagement of CD18 was confirmed in neutrophil-mediated iodination experiments, where iodination induced by TNF-α, fMLP, and GM-CSF was increased 15-, 20-, and 7-fold, respectively, by CD18 cross-linking. Immunoblot experiments demonstrated that TNF-α-induced tyrosine phosphorylation was both accelerated and more intense in neutrophils after cross-linking of CD18. Major tyrosine phosphoprotein products include proteins with approximate molecular masses of 40, 70, and 110 kDa. Genistein (50μM), a selective tyrosine kinase inhibitor, reduced the TNF-α-stimulated respiratory burst by &gt;80% whether or not CD18 was cross-linked. These results affirm the importance of CD18 in adhesion-dependent priming of neutrophil functions and demonstrate that CD18 engagement per se is sufficient to prime neutrophils for cytokine-induced signal transduction mediated by tyrosine phosphorylation.
Genetic approaches to study chemokine function
Authors: Lira Sergio A 
Published: January 2018

Abstract
Chemokines are cytokines capable of inducing Chemotaxis of inflammatory cells in vitro. It is likely that they are also involved in controlling cell migration in vivo, but this and other putative functions have not been properly validated to date. To investigate these functions in vivo, a number of new experimental approaches are required. This mini-review focuses on a set of genetic approaches that can be used to understand chemokine function at the level of the organism. Hopefully, these approaches will help us define the fundamental role of chemokines in development, homeostasis, and disease.
IL-1β primes IL-8-activated human neutrophils for elastase release, phospholipase D activity, and calcium flux
Authors: Brandolini Laura , Bertini Riccardo , Bizzarri Cinzia , Sergi Rita , Caselli Gianfranco , Zhou Dan , Locati Massimo , Sozzani Silvano 
Published: January 2018

Abstract
Interleukin-8 (IL-8), the prototype of the α (i.e., C-X-C branch) chemokine family, induced elastase release in a concentration-dependent manner (50-1000 ng/mL) in cytochalasin B-treated human polymorphonuclear leukocytes (PMNs). This response was potentiated about twofold if PMNs were preexposed to interleukin-1β (IL-1β) at concentrations that were by themselves inactive. The effect of IL-1β was clearly observed after 5 min and was maximal after a 30-min preincubation of the cells. The effect was present over the whole active concentration range of IL-8 and was completely blocked by the presence of IL-1 receptor antagonist. Priming of elastase release by IL-1β was not associated with a change in receptor number or affinity for IL-8. On the contrary, it was correlated with priming of phospholipase D activity and calcium flux activated by IL-8. Preincubation of the cells with ethanol and/or La3+ inhibited IL-8-induced degranulation, suggesting that activation of phospholipase D and increase of [Ca2+]i were important for this response. In contrast, ethanol and La3+ did not decrease the priming effect of IL-1β. IL-8 and IL-1β have been shown to be released by the same cell types and may be concomitantly present at sites of inflammation, giving rise to an amplification of the inflammatory response.
Control of the production of soluble interleukin-4 receptors: implications in immunoregulation
Authors: Femandez-Botran Rafael , Chilton Paula M , Ma Yuhe , Windsor Jana L , Street Nancy E 
Published: January 2018

Abstract
Soluble cytokine receptors (sCR) are generated in vivo through proteolytic cleavage of the membrane-bound receptors or by direct translation of mRNAs specifically encoding the soluble forms. Despite their widespread presence in biological fluids, the physiological role of endogenous sCR as immunoregulatory molecules is not yet well understood. In vivo, exogenous soluble interleukin-4 receptors (sIL-4R) have been shown to have both agonistic and antagonistic effects on IL-4 responses, depending on the relative concentration ratios of sIL-4R to IL-4. In an effort to elucidate the potential role of endogenous sIL-4R in the regulation of IL-4 responses, the mechanisms controlling the production of sIL-4R have been investigated. Although many cell types are able to constitutively produce low levels, production of sIL-4R is significantly up-regulated in vitro by T cell activation and IL-4. The ability of splenic cells to produce sIL-4R and the serum levels of sIL-4R have consistently been found to be increased during immune responses characterized by T cell activation and IL-4 secretion (Th2 responses). In agreement, clones of Th2, but not Th1, cells were found to significantly up-regulate sIL-4R production following antigenic stimulation. However, the production of sIL-4R by Th2 cells appears to be independent from that of IL-4 and can also be induced by cell contact and/or IL-1-dependent pathways. Taken together, these observations suggest that the production of sIL-4R in vivo is closely associated with the secretion of IL-4, and are consistent with the notion that endogenous sIL-4R are involved in the regulation of IL-4 activity during immune responses.
Effect of adenosine on the expression of β2 integrins and L-selectin of human polymorphonuclear leukocytes in vitro
Authors: Thiel M , Chambers J David , Chouker A , Fischer S , Zourelidis C , Bardenheuer Hubert J , Arfors Karl-E , Peter K 
Published: January 2018

Abstract
Adenosine has been shown to inhibit the adhesion of polymorphonuclear leukocytes (PMNL) to the vascular endothelium. Because the underlying molecular mechanisms have not been fully understood, the present study characterizes the effect of adenosine on the expression of adhesion molecules of human PMNL. When PMNL were activated by N-formyl-methionyl-leucyl-phenylalanine the number of cell surface β2 integrins increased fivefold, whereas L-selectin molecules were completely shed. Activation-dependent numerical up-regulation of β2 integrins and shedding of L-selectin were inhibited by exogenously applied adenosine receptor agonists in a concentration-dependent fashion. The rank or-der of potencies of adenosine receptor agonists, measured by the agonists’ half-maximal inhibitory concentrations, revealed that adenosine inhibited the numerical up-regulation of β2 integrins and shedding of L-selectin most likely via an A2(a) receptor site. When extracellular concentrations of endogenously formed adenosine were enhanced by the nucleoside uptake inhibitor dipyridamole, up-regulation of β2 integrins, and shedding of L-selectin was again inhibited. Both effects were reversed by the enzyme adenosine deaminase, which degrades active adenosine to inactive inosine, suggesting that endogenously formed adenosine may play an important role in the regulation of β2 integrins and L-selectin of human PMNL.
Priming of human peripheral blood mononuclear cells with lipopolysaccharides for enhanced arachidonic acid release and leukotriene synthesis
Authors: Surette Marc E , Nadeau Marie , Borgeat Pierre , Gosselin Jean 
Published: January 2018

Abstract
In a previous study, we have shown that the ability of lipopolysaccharides (LPS) to prime isolated neutrophils for enhanced leukotriene B4 (LTB4) synthesis was dependent on the presence of plasma and involved the CD14 antigen. In the present study, we have investigated the priming of human peripheral blood mononuclear cells (PBMC) with LPS for the subsequent release and metabolism of arachidonic acid. When PBMC were incubated with LPS for up to 2 h or when freshly isolated PBMC were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or with LPS alone, little or no synthesis of 5-lipoxygenase products nor arachidonic acid liberation were detected. However, the preincubation of PBMC with IPS for as little as 5 min primed cells for the subsequent synthesis of LTB4 upon stimulation with fMLP. Maximal priming was observed following a 15-min preincubation period and the priming effect was transient as cells preincubated with IPS for 90 min or more were no longer primed for leukotriene synthesis. Monocytes were found to be responsible for the enhanced response to fMLP since purified lymphocytes did not produce LTB4 nor LTC4 in contrast to monocyte-enriched suspensions. The priming for leukotriene synthesis coincided with an increased capacity for the release of free arachidonic acid as measured by mass spectrometry; IPS-primed cells released 8–15 times more arachidonic acid than unprimed cells within 1 min of stimulation with fMLP. Pruning was observed with as little as 0.001-0.01 μg LPS/mL when cells were incubated in the presence of 10% autologous plasma. Interestingly, in the absence of plasma, priming was only observed at IPS concentrations of 0.1 μg/mL or greater. Pretreatment of cells with anti-CD14 antibodies significantly decreased the priming effect observed with 0.01 μg/mL IPS but did not affect pruning with 1 μg/mL IPS. These results indicate that the priming of human PBMC with IPS for the subsequent synthesis of arachidonic acid metabolites via the 5-lipoxygenase pathway is dependent on plasma and CD14 at lower concentrations of IPS (0.001–0.01 μg/mL) but not at IPS concentrations of 0.1 μg/mL or greater.
Cloning and expression of a second human natural killer cell granule tryptase, HNK-Tryp-2/granzyme 3
Authors: Sayers Thomas J , Lloyd Andrew R , McVicar Daniel W , O’Connor Michael D , Kelly Janice M , Carter Clive R D , Wiltrout Theresa A , Wiltrout Robert H , Smyth Mark J 
Published: January 2018

Abstract
Cytotoxic lymphocytes possess a number of serine proteases (granzymes) usually localised in cytoplasmic granules. To date, the DNA sequences of four human granzymes have been reported. A fifth human granzyme (granzyme 3) has been biochemically purified and its N-terminal amino acid sequence has been reported. This enzyme was described as possessing tryptase activity, cleaving synthetic substrates after arginine or lysine. We recently cloned a rat granzyme tryptase (RNK-Tryp-2), and used this cDNA to screen human cDNA libraries. Isolation of cDNA fragments of a human gene could be overlapped to provide a complete cDNA sequence, which we designated HNK-Tryp-2. The N-terminal amino acid sequence deduced from HNK-Tryp-2 was identical to that reported for granzyme 3. This gene appears to be a single copy gene that is expressed in isolated natural killer cells and T cells as well as in tissues containing these cells.
Transforming growth factor-β1–deficient mice: identification of isoform-specific activities in vivo
Authors: Letterio John J , Roberts Anita B 
Published: January 2018

Abstract
A remarkable range of activities has been ascribed to the family of proteins known as transforming growth factor-β (TGF-β). Each plays an important role in development and homeostasis, influencing mesenchymal-epithelial interactions, regulating cellular differentiation, and maintaining control of cell proliferation. Although in vitro comparisons of activity demonstrate a high degree of functional similarity, recent studies of mice with a targeted deletion of the TGF-β1 gene reveal that true isoform-specific activities do exist in vivo and that the three mammalian isoforms are not functionally redundant. This approach has defined a unique role for TGF-β1 in the establishment and maintenance of normal immune function, shed new light on the relevance of endogenous TGF-β1 to the normal wound healing process, and expanded the list of known mechanisms of TGF-β1 activity to include endocrine functions. Thus, the TGF-β1-deficient mouse allows the definition of isoform-specific activities, providing an invaluable window through which to view the principal functions of TGF-β1 in vivo.
Soluble versus cell-bound CD4, CD8 from bronchoalveolar lavage: correlation with pulmonary diagnoses in human immunodeficiency virus-infected individuals
Authors: Willsie Sandra K , Herndon Betty L , Miller Leslie , Dew Michelle 
Published: January 2018

Abstract
Identification and assessment of cell populations in bronchoalveolar lavage (BAL) specimens may be used to follow the course of a disease state or response to specific therapy. Beyond cellular assessment, there are indications that the presence and quantity of soluble surface antigens released from activated cells may lead to improved understanding and facilitated diagnosis of a number of disease states. This study evaluated soluble markers (sCD4 and sCD8) in BAL and serum from HIV-infected individuals undergoing diagnostic bronchoscopy, and compared these values to flow cytometry-quantified BAL and peripheral blood cell CD4 and CD8. Patient pulmonary diagnosis (based on cytology and microbiology) was compared with patient blood and BAL-soluble and cell-bound CD4 and CD8 to determine the relationship of these markers to disease states in this population. Serum sCD8 in patients with fungal infections was significantly elevated above sCD8 in patients with Pneumocystis carinii or pulmonary bacterial infections, p = 0.0001. BAL sCD4/sCD8 ratio was also significantly different in patients with bacterial vs. fungal pulmonary infections, p = 0.01. These findings suggest that soluble markers, particularly elevated sCD8, may be an important indication of pulmonary disease progression in these HIV+ patients with fungal infections.