bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and viral protein interactions regulating IκBα activity during human retrovirus infection
Authors: Hiscott John , Beauparlant Pierre , Crepieux Pascale , DeLuca Carmela , Kwon Hakju , Lin Rongtuan , Petropoulos Louisa 
Published: January 2018

Abstract
NF-κB/Rel transcription factors participate in the activation of numerous genes involved in immune regulation/inflammation including cytokines, cell surface receptors, adhesion molecules, and acute phase proteins. NF-κB activity is controlled by inhibitory proteins, IκBs, that maintain the DNA-binding forms of NF-κB in an inactive state in the cytoplasm. Many viruses, including the human retroviruses HIV-1 and HTLV-1, also utilize the NF-κB/IκB pathway to their transcriptional advantage during viral infection. Our recent studies have focused on the IκBα inhibitor and have characterized several protein interactions that modulate the functional activity of IκBα during human retrovirus infection. In this article, we summarize recent studies demonstrating that (1) chronic HIV-1 infection of human myelomonoblastic PLB-985 cells leads to constitutive NF-κB activity, activated in part due to enhanced IκBα turnover and increased NF-κB/Rel production; (2) HTLV-1 Tax protein physically associates with the IκBα protein in vivo and in vitro and also mediates a 20- to 40-fold stimulation of NF-κB DNA binding activity mediated via an enhancement of NF-κB dimer formation; (3) casein kinase II phosphorylates IκBα at multiple sites in the C-terminal PEST domain and regulates IκBα function; (4) transdominant forms of IκBα, mutated in critical Ser or Thr residues required for inducer-mediated (S32A, S36A) and/or constitutive phosphorylation block HIV LTR trans-activation and also effectively inhibit HIV-1 multiplication in a single cycle infection model; and (5) the amino-terminal 55aa of IκBα (NIK) interacts with the human homologue of dynein light chain 1, a small 9-kDa human homologue of the dynein light chain protein involved in microtubule and cytoskeletal dynamics. Together, our results highlight a number of intriguing molecular interactions between IκBα and cellular or viral proteins that modulate transcription factor activity and nuclear-cytoplasmic flow of host proteins.
Expression and function of the early activation antigen CD69 in murine macrophages
Authors: Marzio Rosa , Jirillo Emilio , Ransijn Adriana , Mauël Jacques , Corradin Sally Betz 
Published: January 2018

Abstract
CD69, a member of the natural killer cell gene complex family of signal transducing receptors, represents one of the earliest activation antigens in human and murine lymphocytes. In contrast, human monocytes may express CD69 in a constitutive fashion. We have evaluated the expression and function of CD69 in murine bone marrow-derived macrophages. CD69 expression as determined by flow cytometry was not constitutive but was induced by stimulation with interferon-γ (IFN-γ) plus bacterial lipopolysaccharide (LPS) or tumor necrosis factor α (TNF-α). Stimulation with LPS alone was equally effective. Infection with the protozoan parasite Leishmania did not induce CD69 expression nor influence CD69 up-regulation by IFN-γ plus LPS. Induction of CD69 expression was significantly inhibited in the presence of prostaglandin E2 or dibutyryl-cAMP. Stimulation of macrophages with anti-CD69 monoclonal antibody in the presence of IFN-γ induced both nitric oxide production and TNF-α release. Moreover, anti-CD69 stimulation of Leishmania-infected macrophages resulted in elimination of the intracellular parasite. These results suggest that CD69 is an activation antigen for murine macrophages and may serve as a signaling receptor for an as yet uncharacterized ligand.
Insulin-stimulated chemokinesis in normal human neutrophils is dependent on D-glucose concentration and sensitive to inhibitors of tyrosine kinase and phosphatidylinositol 3-kinase
Authors: Oldenborg Per-Arne , Sehlin Janove 
Published: January 2018

Abstract
This study shows that D-glucose and insulin, alone and in certain combinations, have chemokinetic effects on neutrophil granulocytes from healthy humans. A stimulatory chemokinetic effect of insulin was present at 40-160 μU/mL insulin but only in the presence of 5 mM, and not at 15 mM, D-glucose. D-Glucose alone dose-dependently increased the neutrophil locomotion, showing a maximum effect at 5–15 mM and a return toward the basal locomotion at 25 mM glucose. Because the stimulatory chemokinetic effects of 5 and 15 mM D-glucose alone were the same, it seems that the high glucose level does not inhibit the basic motile properties of the cells but may generate intracellular signals interfering with the signal transduction underlying the insulin effect. The tyrosine kinase inhibitor, genistein, or the phosphatidylinositol 3-kinase inhibitor, wortmannin, abolished the chemokinetic effect of 160 μU/mL insulin in the presence of 5 mM D-glucose. This indicates that the insulin effect on locomotion is indeed mediated by receptor-associated tyrosine kinase activation and involving phosphatidylinositol 3-kinase.
The effects of pregnancy on autoimmune diseases
Authors: Buyon Jill P 
Published: January 2018

Abstract
Internal gestation of a genetically foreign conceptus challenges the maternal host to circumvent immunological processes that recognize and eliminate nonself molecules. Accordingly, human viviparity involves a wide range of immunological modifications. This review examines the relationship between pregnancy and several autoimmune diseases prevalent in women. Pregnancy is associated with improvement in the clinical signs and symptoms of rheumatoid arthritis in more than 70% of patients. Maternal-fetal disparity in alleles of HLA-DRβl, DQα, and DQβ has been reported to be associated with pregnancies characterized by remission or improvement. These observations suggest that presentation of fetal DQα peptides might correct autoimmunity in patients with RA either by induction of maternal-regulatory T cells, or by affecting the maternal T cell receptor repertoire. In contrast, the course of systemic lupus erythematosus is more variable. Whether flare rates increase during or after pregnancy is unsettled, since individual patient series vary in the characteristics of patients accepted for study and in definitions of flare. Despite a high overall flare rate in some series approaching 60%, recorded flares were usually not severe. Only limited data are available regarding the incidence or outcome for either the mother with scleroderma or her fetus. The extent of diffuse skin disease and systemic involvement, particularly pulmonary, cardiac and renal, may be more important than the duration of the disease; limited disease carries a better prognosis for the mother and fetus. Highly specific autoantibody profiles in the mother (independent of whether she has a clinical disease) are associated with fetal demise and neonatal lupus syndromes, the most serious manifestation of which is isolated congenital heart block. The former is associated with antiphospholipid antibodies and the latter with antibodies directed against SSA/Ro and SSB/La polypeptides.
Human neutrophils are devoid of the integral membrane protein caveolin
Authors: Sengeløv Henrik , Voldstedlund Marianne , Vinten Jørgen , Borregaard Niels 
Published: January 2018

Abstract
The secretory vesicles of human neutrophils are rapidly mobilizable vesicles that contain several GPI-linked proteins, a characteristic feature of caveolae in other cells. To investigate whether secretory vesicles are structurally related to caveolae, we examined human neutrophils for the presence of caveolin, a major constituent of caveolae, by immunoblotting using monoclonal and polyclonal antibodies. Caveolin was not detected in lysates of human neutrophils nor in isolated plasma membrane/light membrane fractions in which secretory vesicles localize. In contrast, caveolin was readily detected in isolated membranes of adipose cells. We conclude that human neutrophils are devoid of caveolin and that secretory vesicles are not related to caveolae nor dependent on caveolae for mobilization.
Expression of macrophage-derived chemokine (MDC) mRNA in macrophages is enhanced by interleukin-1 β, tumor necrosis factor α, and lipopolysaccharide
Authors: Rodenburg R J T , Brinkhuis R F B , Peek R , Westphal J R , van Den Hoogen F H J , van Venrooij W J , van de Putte L B A 
Published: January 2018

Abstract
A cDNA encoding the CC chemokine MDC was isolated from a human macrophage cDNA library by differential hybridization using monocyte- and macrophage-specific cDNA probes. During monocyte to macrophage differentiation in vitro, MDC expression is first detected after 1 day of culturing and reaches maximum levels after 6 days when macrophages have fully matured, as judged from the expression of known macrophage marker genes. Exposure of macrophages to lipopolysaccharide (LPS) results in a dose-dependent increase in MDC mRNA levels, with maximum induction occurring after 6–8 h, whereas expression levels of macrophage inflammatory protein-1α (MIP-1α), MIP-2, interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) respond much faster to LPS. Furthermore, MDC expression in macrophages is enhanced by the inflammatory mediators TNF-α and IL-1β. Similar to other TNF-α/IL-1β-inducible genes, costimulation of macrophages with both cytokines leads to higher MDC expression levels than stimulation with a single cytokine. By contrast, both resting and activated monocytes do not express MDC mRNA.
IgA Fc receptor (CD89) activation enables coupling to syk and Btk tyrosine kinase pathways: differential signaling after IFN-γ or phorbol ester stimulation
Authors: Launay Pierre , Lehuen Agnés , Kawakami Toshiaki , Blank Ulrich , Monteiro Renato C 
Published: January 2018

Abstract
IgA Fc receptors (FcαR) can mediate a variety of inflammatory responses. It has been demonstrated that the FcRγ subunit is critical in mediating signaling through FcαR. We show that aggregation of FcαR on U937 cells and blood neutrophils results in tyrosine phosphorylation of several intracellular proteins, including the FcR γ subunit, p72syk, and Bruton tyrosine kinase (Btk). Syk was found to be associated with FcαR and its phosphorylation was increased in phorbol myristate acetate (PMA)- and interferon-γ (IFN-γ)-treated U937 cells. In contrast, phosphorylation of Btk was only detected after cell treatment with PMA but not IFN-γ. These data indicate that signaling through FcαR γ2 involves at least two subfamilies of tyrosine kinases, syk and Btk. Our results also suggest that activation of tyrosine kinase pathways through FcαR depends on the activation state of the cell. This may be an important regulatory mechanism in IgA-mediated responses at inflammatory sites.
Mast cells produce ENA-78, which can function as a potent neutrophil chemoattractant during allergic airway inflammation
Authors: Lukacs Nicholas W , Hogaboam Cory M , Kunkel Steven L , Chensue Stephen W , Burdick Marie D , Evanoff Holly L , Strieter Robert M 
Published: January 2018

Abstract
The inflammatory response during allergic airway inflammation involves the recruitment of multiple leukocyte populations, including neutrophils, monocytes, lymphocytes, and eosinophils. All of these populations likely contribute to the pathology observed during repeated episodes of allergic airway inflammation. We have examined the role of a human neutrophil-specific chemokine (C-x-C), ENA-78, in a model of allergic airway responses and identified murine mast cells as a cellular source of an ENA-78-like molecule. Within this allergic airway model, neutrophil infiltration into the airway occurs within 4–8 h post-allergen challenge, persists within the airway until 24 h, and resolves by 48 h post-challenge. Neutrophil influx precedes the eosinophil infiltration, which peaks in the airway at 48 h post-allergen challenge. In this study the production of ENA-78 from challenged lungs demonstrated a significant increase in the allergen-, but not vehicle-, challenged lungs. In vivo neutralization of ENA-78 by passive immunization demonstrated a significant decrease in peak neutrophil infiltration at 8 h, with no effect on the eosinophil infiltration at 48 h post-challenge. Because ENA-78 has been shown to be chemotactic for neutrophils and given the involvement of mast cell degranulation in allergic responses, we examined mast cells for the presence of ENA-78. Cultured mast cells spontaneously released ENA-78, but on activation with IgE + antigen, NG-L-arginine methyl ester or compound 48/80 produced significantly increased levels of ENA-78. Supernatants from sonicated MC-9 mast cells induced an overwhelming influx of neutrophils into the BAL by 4 h post-intratracheal injection into mice, suggesting that the mast cell is a significant source of neutrophil chemotactic factors. Mast cell supernatant-mediated neutrophil infiltration was substantially decreased by preincubation of the supernatant with antibodies specific for ENA-78. These data indicate a major neutrophil chemotactic protein produced by mast cells during allergic responses may be mast cell-derived ENA-78.
Regulation of T helper cell differentiation by STAT molecules
Authors: Kaplan Mark H , Grusby Michael J 
Published: January 2018

Abstract
It is now well appreciated that the cytokines interleukin (IL)-12 and IL-4 are important for the generation of Th1 and Th2 cells, respectively. Only recently, however, have the molecular mechanisms by which these cytokines affect Th cell differentiation begun to be defined. Previous work from our laboratory has demonstrated that members of the signal transducer and activator of transcription (STAT) gene family are critical for the differentiation of Th cell subsets. In particular, Stat4-deficient mice show an impairment in the generation of Th1 cells, whereas Stat6-deficient animals do not generate Th2 cells. We have now generated Stat4-Stat6 double-deficient mice to determine whether STAT-independent pathways exist for the development of Th cell subsets. It is surprising that Th1 but not Th2 cells can be generated from double-deficient mice in vitro and these animals are able to mount an in vivo Th1 cell-mediated immune response. These results suggest a model of Th cell differentiation in which Stat4 and Stat6 have different roles in the development of Th cell subsets. J. Leukoc. Biol. 64: 2–5; 1998.
Neutrophils responded to immobilized lipopolysaccharide in the absence of lipopolysaccharide-binding protein
Authors: Nakatomi Kensuke , Aida Yoshitomi , Kusumoto Keisuke , Pabst Michael J , Maeda Katsumasa 
Published: January 2018

Abstract
Lipopolysaccharide (LPS) in solution primes neutrophils for enhanced release of superoxide in response to N-formyl-methionyl-leucyl-phenylalanine. We show that LPS immobilized on polystyrene or polypropylene acted on neutrophils by a mechanism different from that of LPS in solution. Coating the surface with 1% plasma, either before coating with LPS (plasma/LPS) or after coating with LPS (LPS/plasma), was essential to induce the LPS response in neutrophils. However, plasma could be replaced by fibrinogen, type I collagen or type IV collagen, or, to a lesser extent, by fibronectin or vitronectin, which was not true for LPS in solution. About 20% of the LPS added was immobilized on the plastic surfaces, based on its ability to adsorb anti-LPS antibody after extensive washing. The amount of soluble LPS that might have been released from surfaces during the incubation with neutrophils was too low to account for the priming by immobilized LPS. About 13–20 min was needed for neutrophils to become primed after incubation with immobilized LPS. Immobilized LPS induced up-regulation of CD11b/CD18 and latent alkaline phosphatase and also enhanced the adhesive response of neutrophils. Priming by immobilized LPS was inhibited by anti-CD14 antibody or by treatment of neutrophils with the LPS antagonist LA-14-PP. When immobilized LPS was treated with anti-LPS-binding protein (LBP) antibody, the response of neutrophils to LPS/plasma was inhibited but the response to plasma/LPS or fibrinogen/LPS was not. Thus, the LPS in plasma/LPS or fibrinogen/LPS acted on neutrophils in an LBP-independent manner. We conclude that the CD14-dependent LPS receptor system of neutrophils was capable of working in the absence of LBP, but only when LPS was immobilized on a surface coated with protein. J. Leukoc. Biol. 64: 177–184; 1998.
Interferon-α and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells
Authors: Paquette Ronald L , Hsu Nicholas C , Kiertscher Sylvia M , Park Alice N , Tran Lawrence , Roth Michael D , Glaspy John A 
Published: January 2018

Abstract
The diverse roles of interferon-α (IFN-α) in regulating the immune response to infectious agents suggested that it might affect dendritic cell (DC) development. Peripheral blood mononuclear cells cultured with IFN-α and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology and expressed high levels of the class I and II human leukocyte antigens (HLA), B7 costimulatory molecules, adhesion proteins, and CD40. Elevated DC expression of B7-2 and HLA-DR was observed with increasing IFN-α concentrations up to 5000 U/mL. The effects of IFN-α on DC immunophenotype were not reversed by adding neutralizing antibodies against interleukin-4 (IL-4) or tumor necrosis factor α to the cell cultures or by eliminating lymphocytes from the cultures. The addition of IFN-α to cultures containing optimal concentrations of IL-4 and GM-CSF significantly increased the B7-2 and HLA-DR levels above those present on DCs grown in two cytokines. The DCs generated with IFN-α and GM-CSF were potent antigen-presenting cells in allogeneic mixed leukocyte reactions. They also were capable of taking up, processing, and presenting tetanus toxin to autologous T lymphocytes. These results demonstrate an important role for IFN-α in the generation of DCs with potent antigen-presenting capabilities from peripheral blood monocytes. J. Leukoc. Biol. 64: 358–367; 1998.
Antibody-induced engagement of β2 integrins in human neutrophils causes a rapid redistribution of cytoskeletal proteins, Src-family tyrosine kinases, and p72syk that precedes de novo actin polymerization
Authors: Yan Sen Rong , Berton Giorgio 
Published: January 2018

Abstract
β2 Integrins mediate rearrangement of the cytoskeleton and activation of selective cell functions in neutrophils. To elucidate early events following β2 integrin ligation, we analyzed redistribution of cytoskeletal and signaling proteins as a consequence of antibody-induced integrin clustering. Incubation of neutrophils on surface-bound anti-β2 subunit antibodies induced a very rapid (within 1 min) redistribution of the cytoskeletal proteins talin, α-actinin, and paxillin, and the tyrosine kinases p58c-fgr, p53/56lyn, and p72syk to a cell fraction insoluble in Triton X-100. Cytoskeletal and signaling proteins redistribution preceded de novo actin polymerization because cytochalasin B did not inhibit this redistribution. Antibody engagement of all the three distinct β2 integrins (CD11a, CD11b, CD11c) expressed by neutrophils induced redistribution of cytoskeletal proteins and tyrosine kinases. Several tyrosine phosphorylated proteins were also rapidly redistributed as a consequence of β2 integrin engagement and this was not affected by blocking de novo actin polymerization with cytochalasin B. In addition, genistein, an inhibitor of tyrosine kinase activities which strongly reduced protein tyrosine phosphorylation, had no effect on redistribution of cytoskeletal proteins, Src-family kinases, and p72syk. These findings suggest that integrin-dependent cytoskeleton rearrangement in neutrophils occurs in at least two distinct steps and nucleation of some cytoskeletal proteins together with tyrosine kinases precedes rearrangement of the actin-based cytoskeleton and tyrosine kinases activation. On the basis of these and previous findings we propose a model explaining mechanisms of integrin signaling in neutrophils. J. Leukoc. Biol. 64: 401–408; 1998.
P-selectin and MAC-1 mediate monocyte rolling and adhesion to ECM-bound platelets under flow conditions
Authors: Kuijper P H M , Torres H I Gallardo , Houben L A M J , Lammers J-W J , Zwaginga J J , Koenderman L 
Published: January 2018

Abstract
Accumulation of monocyte-derived foam cells in focal areas of the atherosclerotic (A.S.-) lesion is one of the key events in early atherogenesis. Using a flow model for the damaged vessel wall, we examined the ability of ECM-bound platelets to induce monocyte tethering and adhesion. Whereas ECM-proteins alone induced monocyte adhesion only at low shear stresses (&lt;100 mPa), ECM-bound platelets induced monocyte rolling and adhesion at shear stresses up to 240 mPa. Studies with specific antibodies showed that monocyte adhesion to platelets was mainly mediated by P-selectin and monocyte PSGL-1 (maximum inhibition 90%). β2-Integrin blocking CD18 and CD11b antibodies partly inhibited the arrest of rolling cells. Antibodies against other adhesion molecules such as LFA-1, PECAM-1, and β1-integrins had no effect. Even sparsely adhered platelets (~10% coverage of the surface) already strongly supported monocyte tethering. In conclusion, activated platelets present on ECM are a powerful adhesive substrate for monocyte recruitment under flow conditions. J. Leukoc. Biol. 64: 467–473; 1998.
Sulfite is released by human neutrophils in response to stimulation with lipopolysaccharide
Authors: Mitsuhashi Hideki , Nojima Yoshihisa , Tanaka Takaharu , Ueki Kazue , Maezawa Akira , Yano Shintaro , Naruse Takuji 
Published: January 2018

Abstract
Exposure to sulfite, a well-known air pollutant, induces inflammatory reactions characterized by neutrophil infiltration into the airways. Using a simple and sensitive assay for sulfite concentration in biological fluids, we demonstrate herein that human neutrophils released significant amounts of sulfite (1.0 nmol/h/107 cells) in response to lipopolysaccharide (LPS), a major component of bacterial endotoxin. A large proportion of the sulfite release by neutrophils was dependent on inorganic sulfate contained in culture media, suggesting production via the sulfate reducing pathway in this response. We also show that glucocorticoids and FK506 completely inhibit LPS-mediated sulfite release by neutrophils. Given the well-known antimicrobial activities of sulfite, our results suggest that sulfite acts as a neutrophil mediator of host defense. A putative role of sulfite as an endogenous biological mediator is further underscored by the observation that in vivo administration of LPS is associated with a marked increase in the serum concentration of sulfite in Wistar rats. Inhibition of sulfite release by immunosuppressive agents may contribute to increased susceptibility to bacterial infection commonly associated with the administration of these drugs. J. Leukoc. Biol. 64: 595–599; 1998.