bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD38 expression and functional activities are up-regulated by IFN-γ on human monocytes and monocytic cell lines
Authors: Musso Tiziana , Deaglio Silvia , Franco Luisa , Calosso Liliana , Badolato Raffaele , Garbarino Giovanni , Dianzani Umberto , Malavasi Fabio 
Published: September 2022

AbstractHuman CD38, a surface molecule expressed by immature and activated T and B lymphocytes, has been characterized as a molecule transducing activation and proliferation signals, and intervening in adhesion to endothelium via its ligand CD31. CD38 is also a complex ectoenzyme featuring ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities, leading to the synthesis and degradation of cADPR, a Ca+-mobilizing agent. We investigated the effects of monocyte-activating stimuli (IFN-γ, IL-2, LPS, TNF-α, and GM-CSF) on the expression and function of CD38, starting from the observation that human monocytes and the derived lines U937, THP-1, and Mono-Mac-6 bear the molecule on their surface. Our results indicate that IFN-γ is a strong up-modulator of CD38, and IL-2 increases its expression only modestly. LPS, TNF-α, and GM-CSF had no detectable effects. Treatment with IFN-γ produced a dose- and time-dependent up-regulation of CD38 in monocytes and monocytic lines, which was paralleled by increased ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities. Furthermore, CD38 ligation by specific MoAb reduced the IFN-γ-dependent enhancement of monocyte-dynamic adhesion to endothelial monolayers. These findings identify IFN-γ as a modulator of monocytic CD38 expression and indicate that CD38 plays a specific role in the activation and adhesion processes performed by monocytes.
Differential effects of 15-deoxy-Δ12,14-prostaglandin J2 and a peroxisome proliferator-activated receptor γ agonist on macrophage activation
Authors: Guyton Kelly , Bond Robert , Reilly Chris , Gilkeson Gary , Halushka Perry , Cook James 
Published: September 2022

AbstractProstaglandin J2 metabolite15-deoxy-Δ12,14-prostaglandin J2(15-PGJ2) appears to possess anti-inflammatory properties.Unlike other prostaglandins, it has no known plasma membrane receptor.Its effects have been thought to occur through activation of thenuclear peroxisome proliferator-activated receptor γ (PPARγ), but15-PGJ2 may exhibit effects independent of PPARγ. Wehypothesized that 15-PGJ2 modulates macrophage (Mφ)mediator production by acting on cell signaling proteins upstream ofPPARγ. The effects of 15-PGJ2 on bacterial endotoxinLPS-induced rat peritoneal Mφ mediator production were compared withthose of a specific PPARγ agonist, BRL 49653 (BRL), and to theeicosanoids prostaglandin D2 (PGD2) andcicaprost (CICA, a prostacyclin analogue). 15-PGJ2inhibited LPS-induced production of NO, TNF-α, and thromboxaneB2 (TxB2). Equimolar concentrations ofPGD2 and CICA significantly inhibited LPS-stimulatedTNF-α but not NO, and CICA increased TxB2 production. BRLinhibited LPS-induced NO, but augmented LPS-induced TNF-α andTxB2. 15-PGJ2 also inhibited degradation ofLPS-induced IκBα and phosphoactivation of ERK 1/2, but BRL had nosignificant effect on either protein. The cyclopentenone ring2-cyclopenten-1-one also inhibited LPS-induced ERK 1/2 activation;however, neither 15-PGJ2 nor the cyclopentenone inhibitedPMA-induced ERK 1/2 activation. Inhibition of LPS-stimulated mediatorproduction by 15-PGJ2 differed from inhibition byPGD2, CICA, and BRL. The ability of 15-PGJ2 toinhibit LPS-induced Mφ mediator production and cell signaling mayoccur in part through reactivity of its cyclopentenone ring.
Regulation ofl-selectin expression by a dominant negative Ikaros protein
Authors: Christopherson Indu , Piechoki Marie , Liu Guo , Ratner Stuart , Galy Anne 
Published: September 2022

AbstractIkaros family members play critical roles in hematopoietic development, yet molecules regulated by Ikaros proteins remain incompletely characterized. To determine the requirements for functional Ikaros proteins, we overexpressed Ik7, a dominant negative Ikaros protein, in human cell lines and hematopoietic progenitor cells. Ik7 is known to block the normal function of other Ikaros family members in human and mouse cells. Retroviral-mediated overexpression of Ik7 affected two distinct, migratory properties of the CEM T-cell line. Ik7 down-regulated l-selectin cell-surface expression, an effect not a result of increased shedding but of a decrease in l-selectin mRNA levels. Ik7 also reduced the spontaneous migration of CEM T cells in 3-D collagen gels. A reduction in l-selectin, cell-surface expression was also induced by Ik7 in CD34+ hematopoietic progenitor cells. In contrast, the Reh B cell line showed an up-regulation of l-selectin, cell-surface levels when expressing Ik7. For the first time, this study defines an effect of Ikaros proteins in the control of migration-related properties and shows that intact Ikaros proteins are important in a cell type-specific manner for the normal regulation of l-selectin expression.
Phenotypic and functional change of cytokine-activated neutrophils: inflammatory neutrophils are heterogeneous and enhance adaptive immune responses
Authors: Yamashiro Shigeo , Kamohara Hidenobu , Wang Ji-Ming , Yang De , Gong Wang-Hua , Yoshimura Teizo 
Published: September 2022

AbstractPolymorphonuclear leukocytes (PMN) are the most abundant leukocytes, comprising about two-thirds of peripheral blood leukocytes, and play major roles in innate immunity. In addition, PMN play critical roles in the development of adaptive immunity. Recently, defensins and other peptides pre-stored in PMN granules were shown to attract monocytes, dendritic cells, and T cells, leading to the hypothesis that the release of PMN granular peptides may link innate and adaptive immunity. During the past several years, we have focused on an alternative hypothesis that activated PMN further differentiate and acquire new phenotypes and functions that enable them to link the two responses. To test our hypothesis, we have taken local and global approaches and have shown several key findings that support the hypothesis. The findings include the requirement for priming PMN by cytokines to induce the delayed expression of MCP-1/CCL2, a signal for mononuclear cells, and the expression of new cell-surface markers by such cytokine-activated PMN. In the present manuscript, we focus on the phenotypic and functional changes that occur during PMN activation with selected cytokines. The results of our study indicate that inflammatory PMN are heterogeneous and play roles in not only innate but also adaptive immunity in response to stimuli released in injured tissues.
Phosphatidylinositol 3-kinase inhibitors prevent mouse cytotoxic T-cell development in vitro
Authors: Phu Tommy , Haeryfar S M Mansour , Musgrave Bruce L , Hoskin David W 
Published: September 2022

AbstractTo become competent killer cells, CD8+ T cells requirestimulation through signal transduction pathways associated with the T-cell receptor, costimulatory molecules such as CD28, and cytokinereceptors such as the interleukin (IL)-2 receptor. We used wortmanninand LY294002, two inhibitors of phosphatidylinositol 3-kinase (PI3-K), to study the role of PI3-K in mouse cytotoxic T-lymphocyte (CTL)induction in response to mitogenic anti-CD3 antibody. Anti-CD3-inducedCD8+ T-cell proliferation and CTL development wereinhibited dose dependently by both PI3-K inhibitors. IL-2 synthesis byanti-CD3-activated CD8+ T cells was also diminished byPI3-K inhibition. PI3-K inhibition resulted in a modest decrease inanti-CD3-induced CD4+ T-cell proliferation but failed toaffect IL-2 expression by anti-CD3-activated CD4+ T cells. PI3-K inhibition during CTL induction resulted in decreased levels ofmRNAs coding for granzyme B, perforin, and Fas ligand. In addition, CTLinduced in the presence of PI3-K inhibitors failed to conjugatenormally with P815 target cells. Exogenous IL-2 did not reverse theeffects of PI3-K inhibition on CD8+ T-cell proliferationand CTL induction. These results support the conclusion that PI3-Kactivation is involved in T-cell receptor, CD28, and IL-2 receptorsignaling of CD8+ T cells. PI3-K is, therefore, animportant component of multiple signal transduction pathways involvedin CTL generation.
Mechanisms of neutrophil apoptosis in uremia and relevance of the Fas (APO-1, CD95)/Fas ligand system
Authors: Jaber Bertrand L , Perianayagam Mary C , Balakrishnan V S , King Andrew J , Pereira Brian J G 
Published: September 2022

AbstractThe regulation of neutrophil apoptosis in chronic renal failure (CRF) has not been clearly defined. The Fas/FasL system is an important apoptotic regulatory pathway in a wide variety of cells. Fas is a widely expressed cell surface protein that transduces an apoptotic signal after interaction with its natural ligand FasL. In contrast to the extensive tissue distribution of Fas, constitutive expression of FasL is relatively limited. We examined Fas and FasL expression by neutrophils in healthy subjects, patients with CRF, and patients on hemodialysis (HD) and peritoneal dialysis (PD). Fas expression was significantly higher among patients with CRF compared with control subjects, HD patients, and PD patients. FasL expression was significantly higher among patients with CRF compared with control subjects. At 24 h, neutrophil apoptosis was higher among patients with CRF compared with control subjects. Furthermore, high-neutrophil Fas expression was paralleled by a higher sensitivity to Fas-mediated apoptosis. There was a strong correlation between Fas-stimulated apoptosis and creatinine clearance as well as Fas expression. Finally, we found that uremic serum increased the expression of neutrophil-associated Fas and FasL proteins, when compared with normal serum. Further studies are under way to examine the regulation of this pathway in the uremic environment.
Signaling networks regulating β1 integrin-mediated adhesion of T lymphocytes to extracellular matrix
Authors: Woods Melody L , Shimizu Yoji 
Published: September 2022

AbstractT-cell recognition of foreign antigen and migration to specificanatomic sites in vivo involves transient adhesive contacts betweenβ1 integrins expressed on T cells and cell surface proteins orextracellular-matrix components. Engagement of the CD3-T-cell receptor(CD3-TCR) complex initiates a complex signaling cascade involvingcoordinated regulation and recruitment of tyrosine and lipid kinases tospecific regions or microdomains in the plasma membrane. Althoughconsiderable attention has been focused on the signaling events bywhich the CD3-TCR complex regulates transcriptional events in thenucleus, CD3-TCR signaling also rapidly enhances integrin-mediatedadhesion without increasing surface expression of integrins. Recentstudies suggest that CD3-TCR signaling to β1 integrins involvescoordinated recruitment and activation of the Tec family tyrosinekinase Itk by src family tyrosine kinases and phosphatidylinositol3-kinase. These signaling events that regulate integrin-mediated T-celladhesion share both common and distinct features with the signalingpathways regulating interleukin-2 gene transcription.
Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection
Authors: Godaly G , Bergsten G , Hang L , Fischer H , Frendéus B , Lundstedt A-C , Samuelsson M , Samuelsson P , Svanborg Catharina 
Published: September 2022

AbstractNeutrophil migration to infected mucosal sites involves a series of complex interactions with molecules in the lamina propria and at the epithelial barrier. Much attention has focussed on the vascular compartment and endothelial cells, but less is known about the molecular determinants of neutrophil behavior in the periphery. We have studied urinary tract infections (UTIs) to determine the events that initiate neutrophil recruitment and interactions of the recruited neutrophils with the mucosal barrier. Bacteria activate a chemokine response in uroepithelial cells, and the chemokine repertoire depends on the bacterial virulence factors and on the specific signaling pathways that they activate. In addition, epithelial chemokine receptor expression is enhanced. Interleukin (IL)-8 and CXCR1 direct neutrophil migration across the epithelial barrier into the lumen. Indeed, mIL-8Rh knockout mice showed impaired transepithelial neutrophil migration, with tissue accumulation of neutrophils, and these mice developed renal scarring. They had a defective antibacterial defense and developed acute pyelonephritis with bacteremia. Low CXCR1 expression was also detected in children with acute pyelonephritis. These results demonstrate that chemokines and chemokine receptors are essential to orchestrate a functional antimicrobial defense of the urinary tract mucosa. Mutational inactivation of the IL-8R caused both acute disease and chronic tissue damage.
A chimeric MIP-1α/RANTES protein demonstrates the use of different regions of the RANTES protein to bind and activate its receptors
Authors: Blanpain Cédric , Buser Raphaële , Power Christine A , Edgerton Michael , Buchanan Catherine , Mack Matthias , Simmons Graham , Clapham Paul R , Parmentier Marc , Proudfoot Amanda E I 
Published: September 2022

AbstractHuman RANTES (CCL5) and MIP-1α (CCL3) bind and activate several CC chemokine receptors. RANTES is a high-affinity ligand for CCR1 and CCR5, and it binds CCR3 with moderate affinity and CCR4 with low affinity. MIP-1α has similar binding characteristics to RANTES except that it does not bind to CCR3. Here we have generated a chimera of human MIP-1α and RANTES, called MIP/RANTES, consisting of the eight amino terminal residues of MIP-1α preceding the CC motif, and the remainder of the sequence is RANTES. The chimera is able to induce chemotaxis of human monocytes. MIP/RANTES has &gt;100-fold reduction in binding to CCR1 and does not bind to CCR3 but retains full, functional binding to CCR5. It has equivalent affinity for CCR5 to MIP-1α and RANTES, binding with an IC50 of 1.12 nM, and is able to mobilize calcium and induce endocytosis of CCR5 in PBMC in a manner equi-potent to RANTES. It also retains the ability to inhibit R5 using HIV-1 strains. Therefore, we conclude that the amino terminus of RANTES is not involved in CCR5 binding, but it is essential for CCR1 and CCR3.
Potentiation of interferon-γ-stimulated nitric oxide production by retinoic acid in RAW 264.7 cells
Authors: Austenaa Liv M I , Ross A Catharine 
Published: September 2022

AbstractNitric oxide (NO) production is essential for normal immunity. We have examined the capacity of retinoic acid (RA), a pleiotropic hormone necessary for normal immunity, to modulate NO production in RAW 264.7 cells. NO production induced by suboptimal concentrations of interferon-γ (IFN-γ) was significantly greater in cells cultured in low-retinoid medium and treated with all-trans-RA (10−10– 10−6 M, P &lt;0.05), as well as with 9-cis-RA and several retinoids selective for the RA receptor subfamily of nuclear retinoid receptors. Similar results were obtained with lipopolysaccharide and monophosphoryl lipid A as stimuli. The RA-potentiated production of NO was positively correlated with inducible NO synthase (iNOS) protein (r =0.94, P &lt;0.002), although the expression of iNOS mRNA was not altered. We hypothesize that modulation of the macrophage response to suboptimal immune stimuli by physiological concentrations of RA, as observed in these studies, may be important in establishing an optimal balance between T helper (Th) 1- and Th2-mediated immunity.
Mechanism of extracellular release of human neutrophil calprotectin complex
Authors: Voganatsi Alexandra , Panyutich Alexander , Miyasaki Kenneth T , Murthy Rekha K 
Published: September 2022

AbstractCalprotectin is an abundant cytosolic protein complex of humanneutrophils with in vitro extracellular antimicrobial activity. Studiessuggest that calprotectin may be actively secreted from intact HL-60cells and that it can be translocated to polymorphonuclear neutrophil(PMN) cell membranes. To examine whether calprotectin is secretedextracellularly, we incubated soluble and particulate stimuli,including live and heat-inactivated Candida albicans, withwhole blood and measured calprotectin levels in the plasma. We comparedthe release of calprotectin to that of lactoferrin, a protein known tobe secreted by PMNs. Extracellular lactoferrin was detected afterincubation with any of the particulate stimuli. In contrast, asignificant increase in extracellular calprotectin was found only afterincubation with live C. albicans. Specifically, theincrease in extracellular calprotectin correlated directly with aproportional decrease in PMN viability. Our results indicate that humanPMN calprotectin is not secreted extracellularly except as a result ofcell disruption or death.
Effects of macrophage-CSF on pulmonary-macrophage repopulation after bone marrow transplantation
Authors: Bernier Tanja , Tschernig Thomas , Pabst Reinhard , Macke Olaf , Steinmueller Christiane , Emmendörffer Andreas 
Published: September 2022

AbstractPulmonary infections are important causes of morbidity and mortality in immunosuppressed patients after transplantation. After experimental irradiation and syngeneic bone marrow transplantation in mice, macrophages show reduced repopulation in the lung compared with that in other tissues. Macrophages are major microbicidal immune effector cells in host pulmonary defense. Therefore, we examined the role of locally applied cytokines for macrophage repopulation in the lung. An accelerated repopulation of macrophages in the lung was observed after intranasal application of macrophage-colony stimulating factor (M-CSF), but this effect was not enhanced by a combination of M-CSF with interleukin (IL)-3. Local proliferation contributed to this effect. Macrophages in the lung tissue of M-CSF-treated mice displayed greater secretion of IL-6, whereas M-CSF treatment did not enhance the gene expression of other macrophage-specific chemokines. The role of M-CSF treatment was determined in pulmonary murine cytomegalovirus infection using an irradiation/reconstitution model. The M-CSF treatment had no effect on virus load in the lung tissue. However, phosphate-buffered saline-treated mice seemed to develop stronger inflammation after viral infection than M-CSF-treated mice. We conclude that local M-CSF treatment modulates cellular inflammation in the lung during immunosuppression.
Reactive oxygen species mediate angiotensin II-induced leukocyte-endothelial cell interactionsin vivo
Authors: Alvarez Angeles , Sanz Maria-Jesus 
Published: September 2022

AbstractChronically elevated angiotensin II (Ang-II)-induced hypertension is partly mediated by superoxide production. In this study, we have investigated whether the leukocyte-endothelial cell interactions elicited by Ang-II involve reactive oxygen species (ROS) generation. Intravital microscopy within the rat mesenteric microvessels was used. Superfusion (60 min) with Ang-II (1 nM) induced significant increases in leukocyte rolling flux, adhesion, and emigration, which were inhibited by pretreatment with superoxide dismutase or catalase. Dihydrorhodamine-123 oxidation indicated that ROS are primarily produced by the vessel wall. Administration of dimethylthiourea, desferrioxamine, or N-acetylcisteine provoked significant reductions in Ang-II-induced leukocyte-endothelial cell interactions. In addition, a blockade of platelet-activating factor or leukotrienes also attenuated such responses significantly. The results presented indicate that in vivo Ang-II-induced leukocyte recruitment is dependent on the generation of intra- and extracellular ROS. Therefore, the use of anti-oxidants might constitute an alternative therapy for the control of the subendothelial leukocyte infiltration associated with hypertension and atherosclerosis.
Growth factor regulation of neutrophil-endothelial cell interactions
Authors: Zhang Hong , Issekutz Andrew C 
Published: September 2022

AbstractThe effects of the angiogenic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on human polymorphonuclear leukocyte (PMNL)-endothelial cell adhesion and transendothelial migration (TEM) were investigated. Stimulation of human umbilical vein endothelial cells by VEGF or bFGF for 18 h up-regulated intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 expression and significantly increased PMNL adhesion and TEM in response to complement fragment 5a (C5a) or interleukin (IL)-8. In contrast, continued exposure to bFGF (24 h–6 days) down-regulated basal and IL-1- or tumor necrosis factor (TNF)-induced intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin expression as well as PMNL adhesion and TEM. These effects could be reversed by introduction of high concentrations of TNF-α, C5a, or IL-8. None of these inhibitory effects was observed with VEGF. The acute effects of bFGF and VEGF may facilitate PMNL emigration during acute inflammation, but continued bFGF production may have anti-inflammatory actions during chronic inflammation, angiogenesis, and tumor defense by inhibition of endothelial activation for leukocyte recruitment.
Early effects of insulin-like growth factor-1 in activated human T lymphocytes
Authors: Brocardo Mariana G , Schillaci Roxana , Galeano Adriana , Radrizzani Martín , White Verónica , Guerrico Anatilde González , Santa-Coloma Tomás A , Roldán Alicia 
Published: September 2022

AbstractThis study evaluates the effects of insulin-like growth factor (IGF)-1 receptor (IGF-1R) down-regulation in stimulated T lymphocytes by investigating the expression of early activation proteins CD69, CD25, and interleukin (IL)-2. We found that IGF-1 does not modify CD69 expression but increases transcription and protein synthesis of CD25 and IL-2. The lowest level of IGF-1R detected after 15 min of activation suggested that the effects of IGF-1 occur at the initiation of cell activation. The activation of IGF-1R was confirmed by IGF-1R phosphorylation and increased phosphorylation of microtubule-associated protein kinase. We also detected the alternative IGF-1 transcripts Ea, with paracrine/autocrine regulation, and Eb, with endocrine regulation, in Jurkat cells and in quiescent T lymphocytes, and we detected IGF-1 protein in the culture medium after stimulation. These data suggest that the proliferative effects of IGF-1 on T lymphocytes include both autocrine/paracrine and endocrine processes.
Negative regulation of cytokine signaling
Authors: Greenhalgh Christopher J , Hilton Douglas J 
Published: September 2022

AbstractCytokines use complex signaling cascades to elicit their biological effects, many of which involve phosphorylation as a mechanism of activation. Rapid and efficient attenuation of cytokine signals is crucial to maintaining regulation of these processes and to preventing toxic side effects. Phosphatases have been shown to be involved in these regulatory processes, but more recent research has seen the discovery of two new families of negative regulators, the suppressor of cytokine signaling (SOCS) and protein inhibitors of signal transducer and activator of transcription (STAT) (PIAS) protein families. SOCS proteins are induced by and inhibit many cytokine-signaling systems in a classic negative-feedback loop, and the generation of transgenic and knockout models has greatly increased our understanding of their physiological functions. PIAS proteins interact with the transcriptional mediators of cytokine action, the STATs, to suppress their DNA-binding activity. These three classes of molecules form what is now emerging as an integrated system for deactivating cytokine signaling at a number of levels, from the receptor to the transcription factor.