bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the mouse calcium-binding proteins, MRP 8 and MRP 14, in Schistosoma mansoni-induced granulomas: biochemical and functional characterization
Authors: Yang Tzung-Horng , Tzeng Sinfu , Cheng I , Burnett Mark G , Yoshizawa Yusuke , Fukuyama Kimie , Lee Sheng-Chung , Epstein William L 
Published: January 2018

Abstract
Granuloma Initiation factor (GIF), which elicits a granulomatous reaction in naive murine skin, contains low-molecular-weight proteins partially purified from organized granulomas developed in livers of mice with schistosomiasis. In this study, we found that 10- and 14-kDa proteins in the GIF are highly homologous to mouse migration inhibitory factor-related protein (MRP) 8 and MRP 14. Compared with the N-terminal amino acid sequence deduced from each corresponding cDNA, the 10-kDa protein from the granuloma lacks the first methionine, whereas the 14 kDa misses methionine, alanine, and asparagine. Immunohistochemically, cells expressing MRP 8 and MRP 14 considerably increased in different murine tissues after Schistosoma mansoni infection and concentrated in liver around the dilated bloodvessels and at the edge of granulomas. The staining of differentiated macrophages and epithelioid cells located in the center of the granulomas was negative. Immunoreactivity of peritoneal exudate cells also was found to gradually disappear with time in cell culture. Furthermore, in vivo effects of the recombinant proteins in murine skin were described histologically. Both MRPs caused severe infiltration of neutrophils and monocytes during 7–14 days. The reaction resulting from individual MRP implantation became minimal after 50 days but inoculation of the Ca2+-dependent heterodimers showed an extensive eosinophil accumulation.
Signaling mechanisms and the activation of leukocyte integrins
Authors: Newton Rebecca A , Thiel Martin , Hogg Nancy 
Published: January 2018

Abstract
Myeloid cells and lymphocytes primarily circulate in the vascular system but move into the tissues in response to inflammatory signals. Such a mobile lifestyle necessitates the continual making and breaking of cell and cell matrix contacts; the receptors known as the integrins are well suited as mediators of this transient adhesiveness. In general, leukocyte integrins are not constitutively active but become adhesive in response to signaling through other membrane receptors. Candidate receptors for receiving the activating signals are the seven membrane-spanning receptors that are found on all leukocytes. The identity of the signals, however, that are responsible for triggering integrin adhesion in vivo and for promoting directed leukocyte movement into tissues remains incompletely resolved.
Rapid induction of neutrophil apoptosis by sulfasalazine: implications of reactive oxygen species in the apoptotic process
Authors: Akahoshi Tohru , Namai Rie , Sekiyama Naho , Tanaka Sumiaki , Hosaka Shigeru , Kondo Hirobumi 
Published: January 2018

Abstract
Accumulating evidence indicates that neutrophils are crucially involved in the pathogenesis of inflammatory bowel diseases and rheumatoid arthritis. We therefore investigated the effect of sulfasalazine (SSZ), which is widely used in the treatment of these diseases, on neutrophil apoptosis in vitro. The apoptosis of neutrophils was determined by morphology, a DNA histogram of propidium iodide-stained nuclei, and DNA fragmentation. SSZ rapidly accelerated the rate of spontaneous neutrophil apoptosis within clinically relevant concentrations. This effect is unique to neutrophils because other types of leukocytes and a number of leukocyte cell lines are resistant to SSZ. Neutrophil apoptosis caused by SSZ was abrogated by a tyrosine kinase inhibitor, a protein kinase A inhibitor, and antioxidants. The subsequent results provided pharmacological evidence that the phosphorylation of tyrosine kinase and protein kinase A and generation of reactive oxygen species are involved in SSZ-mediated neutrophil apoptosis. These data suggest that SSZ-induced neutrophil apoptosis may account, in part, for the clinical benefits of SSZ on inflammatory bowel diseases and rheumatoid arthritis.
Anti-inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant-induced signal transduction
Authors: Debol Steven M , Herron Michael J , Nelson Robert D 
Published: January 2018

Abstract
Dapsone has clinical utility as an anti-inflammatory agent but the mechanism of this action remains unknown. We have previously reported that dapsone inhibits β2 integrin (CD11b/CD18) -mediated adherence of human neutrophils in vitro and now describe studies designed to discover how dapsone-mediated inhibition of this neutrophil function occurs. Results indicate that dapsone interferes with the activation or function of the G-protein (Gi type) that initiates the signal transduction cascade common to chemotactic stimuli. They also show that dapsone-mediated suppression of this pathway inhibits the generation of second messengers essential to the activation of β2 integrin molecules, as well as respiratory and secretory functions of neutrophils exposed to chemoattractants. We propose that the inhibition of chemoattractant-induced signal transduction by dapsone suppresses neutrophil recruitment and local production of toxic respiratory and secretory products in the affected skin of dermatitis herpetiformis and other neutrophilic dermatoses.
Transcriptional regulation in the immune system: all roads lead to AP-1
Authors: Foletta Victoria C , Segal David H , Cohen Donna R 
Published: January 2018

Abstract
The mechanisms regulating the development and function of the immune system are diverse and complicated. The signaling pathways and target genes that become activated upon cell-surface stimulation are currently being defined, and transcription factor activator protein 1 (AP-1) is proving to be an important regulator of nuclear gene expression in leukocytes. In vitro and in vivo studies have demonstrated that AP-1 expression is induced after a diverse range of stimuli and that AP-1 contributes to the regulation of a large number of genes. In this review we will examine the role of AP-1 during leukocyte activation and differentiation in the immune system.
Gallium arsenide differentially affects processing of phagolysosomal targeted antigen by macrophages
Authors: Lewis Timothy A , Hartmann Constance B , McCoy Kathleen L 
Published: January 2018

Abstract
Gallium arsenide, a semiconductor utilized in the electronics industry, causes immunosuppression in animals. The chemical's effect on macrophages to process antigen for activating pigeon cytochrome-specific helper T cell hybridoma was investigated. Mice were administered 200 mg/kg gallium arsenide or vehicle intraperitoneally. Five-day exposure suppressed processing by splenic macrophages but augmented processing by thioglycollate-elicited and resident peritoneal macrophages. Cytochrome coupled to latex beads was targeted to phagolysosomes to examine processing in lysosomes. Cytochrome beads required phagocytosis for processing and were located in phagolysosomes. Gallium arsenide did not alter the phagocytic ability of macrophages. Peritoneal macrophages normally processed the targeted antigen, indicating that gallium arsenide influenced compartment(s) preceding lysosomes. However, the processing efficiency of exposed splenic macrophages depended on the size of particulate cytochrome, suggesting that processing varied in phagolysosomes of different sizes. Gallium arsenide impacted different intracellular compartments in these macrophages, perhaps contributing to systemic immunotoxicity and local inflammation caused by exposure.
Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions
Authors: Sugisaki Katsunori , Dannenberg Arthur M , Abe Yasuharu , Tsuruta Junji , Su Wei-Juin , Said Waheeda , Feng Lili , Yoshimura Teizo , Converse Paul J , Mounts Phoebe 
Published: January 2018

Abstract
To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL-1β, TNF-α, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN-γ, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive. In general, MCP-1 and TNF-α proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response.
Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants
Authors: O'Neill Luke A J , Greene Catherine 
Published: January 2018

Abstract
Interleukin-1 (IL-1) is a central regulator of the immune and inflammatory responses. Recently, significant advances have been made in the area of IL-1 receptors and IL-1 signal transduction. A family of proteins has been described that share significant homology in their signaling domains with the Type I IL-1 receptor (IL-1RI). These include the IL-1 receptor accessory protein (IL-1AcP), which does not bind IL-1 but is essential for IL-1 signaling; a Drosophila protein Toll; a number of human Toll-like receptors (hTLRs); the putative IL-18/IL-1-γ receptor IL-1Rrp (IL-1 receptor-related protein); and a number of plant proteins. All appear to be involved in host responses to injury and infection. These homologies also extend to novel signaling proteins implicated in IL-1 action. Two IL-1 receptor-associated kinases, IRAK-1 and IRAK-2, which have homologs in Drosophila (Pelle) and plants (Pto), have been implicated in the activation of the transcription factor, nuclear factor κB (NF-κB). IRAK-1 has also been implicated in AP1 induction, Jun amino-terminal kinase (JNK) activation, and IL-2 induction. It recruits the adapter protein TRAF6 to the IL-1 receptor complex via an interaction with IL-1AcP. TRAF6 then relays the signal via NF-κB-inducing kinase (NIK) to two I-κB kinases (IKK-1 and -2), leading to NF-κB activation. Progress has also been made on other IL-1-responsive kinases, including JNK and p38 MAP kinase, with the latter having a role in multiple responses to IL-1. The remarkable conservation between diverse species indicates that the IL-1 system represents an ancient signaling machine critical for responses to environmental stresses and attack by pathogens.
The SOCS proteins: a new family of negative regulators of signal transduction
Authors: Nicholson Sandra E , Hilton Douglas J 
Published: January 2018

Abstract
The negative regulation of cytokine signaling, with the exception of the tyrosine phosphatases, is not widely understood. We recently identified a new family of negative regulators by retroviral expression of hematopoietic cDNA library in the monocytic leukemic cell line, M1. This was coupled with selection for cells that were no longer able to differentiate in response to interleukin-6. From this screen, SOCS-1 was cloned and was shown to arrest cytokine signaling by binding to and inhibiting the intrinsic enzymatic activity of the JAK family of protein tyrosine kinases. SOCS-1 expression is induced in response to a range of cytokines and as such is thought to form part of a classic negative feedback loop. The SOCS family of proteins is linked by the presence of a conserved carboxy-terminal domain termed the SOCS box and now encompasses five distinct protein groups on the basis of the structural elements found amino-terminal to the SOCS box: (1) those that contain SH2 domains, (2) those that contain WD-40 repeats, (3) ankyrin repeats, (4) SPRY domains, and (5) GTPase domains. As yet the function of the SOCS box remains unknown, but given the level of conservation within such diverse proteins, it is likely to have a broadly similar role in each.
γδ T cells present antigen to CD4+ αβ T cells
Authors: Collins Robert A , Werling Dirk , Duggan Sara E , Bland A Patricia , Parsons Keith R , Howard Christopher J 
Published: January 2018

Abstract
γδ and αβ TCR+ T cells share many properties and their interactions are likely to be coordinated and regulated. We provide evidence that cattle γδ T cells are able to present antigen to CD4+ T cells. To help elucidate their function γδ T cell lines were propagated for extensive characterization. Cells expressed high levels of MHC class II and production of costimulatory molecules as evidenced by the binding of a CTLA-4 fusion protein and synthesis of CD80 transcripts. These properties and the presence of a well-developed endosomal compartment indicated the cells might function as antigen-presenting cells. Resting CD4+ T cells from calves immunized with ovalbumin or respiratory syncytial virus-antigen proliferated in response to γδ T cells pulsed with antigen that appeared to be endocytosed via clathrin-coated pits or specific receptors.
Cloning and sequencing of the bovine flavocytochrome b subunit proteins, gp91-phox and p22-phox: comparison with other known flavocytochrome b sequences
Authors: Davis Angela R , Mascolo Patrice L , Bunger Peggy L , Sipes Karen M , Quinn Mark T 
Published: January 2018

Abstract
Neutrophils play an essential role in the cellular defense of the bovine mammary gland and compromised leukocyte function has been linked to the development of bovine mastitis. During mastitis, large numbers of leukocytes migrate into the mammary tissues where they become activated, resulting in the assembly of neutrophil membrane and cytosolic proteins to form a superoxide aniongenerating complex known as the NADPH oxidase. The key membrane-associated component of the NADPH oxidase is flavocytochrome b, which is a heterodimer of p22-phox and gp91-phox. Currently, only the human, porcine, murine, and rattus p22-phox and the human, porcine, and murine gp91-phox gene sequences are known. Because of the important role neutrophils play in bovine host defense, we carried out studies to clone, sequence, and analyze expression of bovine flavocytochrome b. Using polymerase chain reaction cloning techniques and a bovine spleen cDNA library we have cloned both of the bovine flavocytochrome b subunits, p22-phox and gp91-phox. Comparison of the bovine sequences with those of other species also revealed important information regarding key structural features of gp91-phox and p22-phox, including location of putative glycosylation sites. This study greatly contributes to our understanding of the potential functional sites of the flavocytochrome b subunits as well as providing information that can be used to study the role of neutrophils in bovine inflammatory diseases such as mastitis. J. Leukoc. Biol. 64: 114–123; 1998.
Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor
Authors: Lane Kirk B , Egan Brian , Vick Sherell , Abdolrasulnia Rasul , Shepherd Virginia L 
Published: January 2018

Abstract
The mannose receptor is a single polypeptide transmembrane glycoprotein expressed on the surface of macrophages that binds and internalizes soluble and particulate ligands. Physiological ligands for this receptor are pathogens, such as mycobacteria, and extracellular acid hydrolases and peroxidases. Expression of the mannose receptor is tightly linked to the functional state of the macrophage: the receptor appears during differentiation, is increased by macrophage deactivating agents, and is reduced in the presence of macrophage activating agents. Studies of the mechanisms underlying these regulatory processes have been hampered by the lack of a stable cell line that expresses a functional and appropriately regulated mannose receptor. In this study we describe expression and modulation of the mannose receptor by the rat alveolar cell line NR8383. Similar amounts of the mannose receptor ligand horseradish peroxidase were internalized by both NR8383 cells and alveolar macrophages. In addition, NR8383 cells expressed immunoreactive mannose receptor protein and mannose receptor mRNA as detected by Northern analysis. Regulation studies showed that mannose receptor expression was regulated at the levels of activity, protein, and mRNA in NR8383 cells similarly to regulation in primary rat macrophages. In addition, NR8383 cells could be successfully transfected with a luciferase reporter gene, providing the transfectable, mannose receptor-positive macrophage cell line. These results support the hypothesis that NR8383 cells potentially represent the best current macrophage cell line for studying various aspects of macrophage function, and are particularly critical in studies of regulation of the mannose receptor, a key receptor in host defense and immune regulation. J. Leukoc. Biol. 64:345–350; 1998.
Granulocyte colony-stimulating factor activates a 72-kDa isoform of STAT3 in human neutrophils
Authors: Chakraborty Arup , Tweardy David J 
Published: January 2018

Abstract
Granulocyte colony-stimulating factor (G-CSF) signaling involves activation of STATs, proteins that serve the dual function of signal transduction and activation of transcription. We previously demonstrated that G-CSF activated a distinct Stat3-like protein in immature and mature normal myeloid cells, StatG. StatG in normal immature human myeloid cells, i.e. adult CD34+ bone marrow cells, was composed of Stat3β. This investigation was undertaken to determine the composition of StatG in mature normal human myeloid cells, i.e. polymorphonuclear neutrophilic granulocytes (PMN). These studies revealed that the major protein in extracts of PMN activated by G-CSF to bind the high-affinity serum-inducible element (hSIE) is a 72-kDa protein that cross-reacts with Stat3 monoclonal antibody, which we have designated Stat3γ. Stat3γ is derived from Stat3α by limited proteolysis and lacks the carboxyl-terminal portion of Stat3α. Because this region of Stat3α is involved in transcriptional activation, our findings suggest the possibility that Stat3γ may be transcriptionally inactive and may compete with Stat3α for Stat3 binding sites in these terminally differentiated myeloid cells. J. Leukoc. Biol. 64: 675–680; 1998.
Chemokines: signal lamps for trafficking of T and B cells for development and effector function
Authors: Kim Chang H , Broxmeyer Hal E 
Published: January 2018

Abstract
Chemokines can act as signal lamps for trafficking of lymphocytes at the important crossing points of lymphoid tissues. Lymphoid progenitors at different differentiation stages are differentially localized in primary lymphoid tissues and have differential responsiveness to thymic or bone marrow chemokines: SDF-1, CKβ-11/MIP-3β/ELC, SLC/6Ckine/Exodus2, MIP-1β, and TECK. Naive T cells and B cells circulate to secondary lymphoid tissues for possible activation. Chemokines, SDF-1, SLC/6Ckine/Exodus2, CKβ-11/MIP-3β/ELC, BLC/BCA-1, and DC-CK1/PARC, are expressed in the specialized microenvironments of secondary lymphoid tissues and regulate the migration of naive lymphocytes. Effector lymphocytes express a different set of chemokine receptors from naive lymphocytes. T helper (Th) 0 and 1 cells predominantly express CXCR3 and CCR5, whereas Th2 cells express CCR3, CCR4, and CCR8, which, with other factors such as expression patterns of adhesion molecules, likely determine the tissue- specific infiltration of effector lymphocytes. J. Leukoc. Biol. 65: 6–15; 1999.
Granulocyte-macrophage colony-stimulating factor modulates tapasin expression in human neutrophils
Authors: Ouakfaoui Souad El , Heitz Dominique , Paquin Robert , Beaulieu André D 
Published: January 2018

Abstract
Differential display-polymerase chain reaction (DD-PCR) was used to evaluate changes in mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) treated human neutrophils to better understand how this cytokine affects the functions of neutrophils at the molecular level. Although a variety of cDNA fragments were identified as modulated by GM-CSF with the use of DD-PCR, one fragment in particular, NGS-17 (neutrophil GM-CSF-stimulated fragment #17), was characterized. The NGS-17 fragment hybridized to a 3.8-kb mRNA that encodes for a protein of a predicted molecular mass of 47.6 kDa. After cloning and sequencing, this gene was found to code for the recently sequenced tapasin or TAP-A protein. Immunoprecipitation and immunoblotting studies using anti-tapasin antibodies showed that tapasin is expressed in neutrophils and is associated with the MHC class I-TAP complex. Moreover, tapasin expression was found to be induced by dimethyl sulfoxide and by retinoic acid in HL-60 cells. This is the first report on the expression of tapasin in human neutrophils. It provides novel information, at the molecular level, on how GM-CSF enhances the functions of these cells. J. Leukoc. Biol. 65: 205–210; 1999.
Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells
Authors: Zhang Shuli , Mantel Charlie , Broxmeyer Hal E 
Published: January 2018

Abstract
Flt3 ligand (FL) is an early-acting potent co-stimulatory cytokine that regulates proliferation and differentiation of a number of blood cell lineages. Its receptor Flt3/Flk2 belongs to class III receptor tyrosine kinases that also include the receptors for colony-stimulating factor 1, Steel factor, and platelet-derived growth factor. Using CSF-1 receptor/Flt3 chimeras, two groups have characterized some of the post-receptor signaling events and substrate specificity of murine Flt3 receptor. However, there are few studies on the signaling pathway through human Flt3. We examined human Flt3 signaling pathways in a murine IL-3-dependent hematopoietic cell line Baf3, which stably expresses full-length human Flt3 receptor. This subline proliferates in response to human FL. Like the chimeric murine Flt3, human Flt3 undergoes autophosphorylation, associates with Grb2, and leads to tyrosine phosphorylation of Shc on ligand binding. We found that SHP-2, but not SHP-1, is tyrosine-phosphorylated by FL stimulation. SHP-2 does not associate with Flt3, but binds directly to Grb2. SHIP is also tyrosine-phosphorylated and associates with Shc after FL simulation. We further examined the downstream signaling pathway. FL transiently activates MAP kinase. This activation could be blocked by PD98059, a specific MEK inhibitor. PD98059 also blocked cell proliferation in response to FL. These results demonstrate that SHP-2 and SHIP are important components in the human Flt3 signaling pathway and suggest that SHP-2 and SHIP, by forming complexes with adapter proteins Grb2 and Shc, may modulate MAP kinase activation, which may be necessary for the mitogenic signaling of Flt3. J. Leukoc. Biol. 65: 372–380; 1999.