bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice
Authors: Ishimori Naoki , Iwabuchi Kazuya , Fujii Satoshi , Watano Keiko , Iwabuchi Chikako , Ato Manabu , Chiba Hitoshi , Tanaka Shinya , Kitabatake Akira , Onoé Kazunori 
Published: September 2022

AbstractAtherosclerosis involves inflammatory processes between vasculartissues and hematocytes with a hyperlipidemic background. To examinewhether variations of hematocytes constitute one of the geneticcomponents in atherosclerosis, irradiated apolipoprotein E(apoE)-deficient (apoE−/−) mice with hypercholesterolemiaand preexisting atherosclerotic lesions were reconstituted withmixed bone marrow cells (BMC) from syngeneic and wild-type(apoE+/+; atherosclerosis-resistant SJL or -susceptibleB10.S) mice. Stable mixed allogeneic chimeras with small amounts ofserum apoE were established without any detrimentalcomplications. Compared with untreated apoE−/− miceor apoE−/− mice transplanted with syngeneic BMC alone, significant reduction of the cholesterol level and significant lesionregression were observed in the mixed chimeras. Furthermore, mixedchimeras given SJL BMC showed marked reductions in numbers of lesionscompared with those reconstituted with B10.S BMC. Cholesterol levels inthe former SJL chimeras, however, were significantly higher than thosein the latter B10.S chimeras. These findings indicate that theresistance of SJL to atherosclerosis resides in the bone marrow-derivedcells.
Blood mononuclear cells induce regulatory NK T thymocytes in anterior chamber-associated immune deviation
Authors: Wang Yafei , Goldschneider Irving , O'Rourke James , Cone Robert E 
Published: September 2022

AbstractInjection of antigen into the anterior chamber (AC) of the eye, animmunologically privileged site, is associated with the inductionof immune deviation, as evidenced by T helper cell (Th) 1 to Th2 cellpolarization. We recently demonstrated that AC-associated immunedeviation (ACAID) is a thymus-dependent phenomenon initiated by the formation of regulatory α,β T-cell receptor-positiveCD4− CD8− thymocytes(THYregs). In this study, the afferent and efferent limbsof this immunoregulatory loop were traced from peripheral blood to thethymus and then to the spleen by adoptive-transfer assays. The resultsdemonstrate that (1) F4/80+ CD1+ peripheralblood mononuclear cells from mice whose ACs were injected withtrinitrophenol-bovine serum albumin induce the appearance ofnatural killer (NK) 1.1+ THYreg innaïve recipients within 24 h of intravenous infusion; (2)these NK THYregs induce (or generate) suppressor-effector Tcells in the spleens of adoptive recipients; (3) thesesuppressor-effector spleen cells, but not the NK THYregsthemselves, directly inhibit the expression of delayed-typehypersensitivity in sensitized recipients; and (4) peripheral bloodmononuclear cells from AC-injected mice do not induce ACAID inthymectomized recipients. These results confirm our hypothesis thatACAID is a model of centrally induced dominant tolerance mediated byCD-1-dependent NK T cells of recent thymic origin. The results alsoprovide evidence of a novel tolerance induction pathway by whichblood-borne antigen-presenting cells generated by antigen injectioninto an immunologically privileged site transport antigen to the thymusand induce the formation and export of THYreg.
Eotaxin promotes eosinophil transmigration via the activation of the plasminogen-plasmin system
Authors: Ferland Claudine , Guilbert Martin , Davoine Francis , Flamand Nicolas , Chakir Jamila , Laviolette Michel 
Published: September 2022

AbstractThe effect of eotaxin, a potent eosinophil chemotactic factor, on eosinophil transmigration through a reconstituted basal membrane (Matrigel®) was evaluated. Eotaxin induced significant eosinophil transmigration in the presence of 10% fetal bovine serum (FBS) and interleukin-5. Its effect was optimal at 0.01 μM, and it plateaued at 18 h. Eotaxin's effect was greater with eosinophils from asthmatic subjects (61.1 ± 3.4%) than with eosinophils from normal subjects (38.7 ± 4.2%) (P &lt; 0.001). Inhibition of metalloproteinases decreased eotaxin-induced transmigration by ≤10.4%, whereas inhibition of the plasminogen-plasmin system decreased eotaxin's effect by ≤44.4% (P = 0.0002). Moreover, eotaxin-induced transmigration was largely diminished in medium with low concentrations of serum [0.5% FBS: 6.1 ± 2.4%; 10% FBS: 40.2 ± 5.8% (P = 0.0001)] but returned to its initial level with the addition of plasminogen (2 U/mL) to 0.5% FBS (43.1 ± 6.5%). These data show that eotaxin is an efficient promoter of eosinophil transmigration in vitro, that it is more potent with cells from asthmatics than with normal cells, and that its effect depends predominantly on the activation of the plasminogen-plasmin system.
Modulation of death receptor-mediated apoptosis in differentiating human myeloid leukemia HL-60 cells
Authors: Vondráček Jan , Sheard Michael A , Krejčí Pavel , Minksová Kateřina , Hofmanová Jiřina , Kozubík Alois 
Published: September 2022

AbstractDifferentiating myeloid cells may become resistant to various apoptotic stimuli. In the present study, dimethyl sulfoxide (DMSO) and all-trans retinoic acid (ATRA) were found to modulate the sensitivity of HL-60 cells to death receptor-mediated apoptosis in a time-dependent manner. During the early stages of differentiation, DMSO treatment increased the response of HL-60 cells to tumor necrosis factor α; (TNF-α), but enhanced responsiveness was lost during later differentiation stages. In contrast, ATRA treatment induced resistance to TNF-α-induced apoptosis. HL-60 cells were resistant to Fas-mediated apoptosis but were sensitized by culturing in serum-free conditions. Similar to its effect on TNF-α sensitivity, DMSO pretreatment augmented the response to Fas-mediated signaling, which coincided with increased expression of Fas on DMSO-pretreated cells. However, during the later stages of DMSO-induced differentiation, sensitivity to anti-Fas antibody-induced apoptosis declined significantly, although Fas expression was still elevated. The reduced sensitivity to anti-Fas treatment partially correlated with increased Fas-associated phosphatase-1 mRNA expression. Thus, regardless of either Fas up-regulation or potentiation of TNF-α-mediated apoptosis during early DMSO-induced differentiation, a slow increase in resistance to apoptosis mediated through these death receptors occurs during DMSO-induced differentiation, which contrasts with the rapid induction of resistance following treatment with ATRA.
Role of mitogen-activated protein kinases in the differential regulation of interleukin-2 by cannabinol
Authors: Jan Tong-Rong , Kaminski Norbert E 
Published: September 2022

AbstractCannabinoids can paradoxically regulate interleukin-2 (IL-2) expressioneither positively or negatively. This study investigated the mechanismresponsible for cannabinol-mediated IL-2 modulation. In primary murinesplenocytes and EL4.IL-2 T cells, the contrasting effects of cannabinolon IL-2 secretion depended on the magnitude but not the mode of T-cellactivation. Suboptimal activation of T cells in the presence ofcannabinol produced an enhancement of IL-2 secretion, which wasparalleled by an increase in nuclear phospho-extracellular-regulatedkinase (ERK) 1/2. In contrast, T cells activated with stimulithat were optimized to induce maximal IL-2 secretion elicited a markedsuppression in the production of this cytokine when cultured in thepresence of cannabinol. Moreover, cannabinol-mediated enhancement of IL-2 secretion by splenocytes was attenuated to various degrees bystaurosporine, Ro-31-8220, and KN93. These results suggest that theenhancement of IL-2 secretion by cannabinol is associated with anincrease in ERK mitogen-activated protein kinase, which is proteinkinase C and calmodulin-kinase dependent.
Identification and characterization of human eosinophil cationic protein by an epitope-specific antibody
Authors: Boix Ester , Carreras Esther , Nikolovski Zoran , Cuchillo Claudi M , Nogués M Victòria 
Published: September 2022

AbstractThe eosinophil cationic protein (ECP) is a basic secretion proteininvolved in the immune response system. ECP levels in biological fluidsare an indicator of eosinophil-specific activation and degranulationand are currently used for the clinical monitoring and diagnosis ofinflammatory disorders. A polyclonal epitope-specific antibody has beenobtained by immunizing rabbits with a conjugated synthetic peptide. Asequence corresponding to a large exposed loop in the human ECPthree-dimensional structure (D115–Y122) was selected as a putativeantigenic epitope. The antibody was purified on an affinity columnusing recombinant ECP (rECP) as antigen. The antibody (D112–P123 Ab)specifically recognizes rECP and its native glycosylated andnonglycosylated forms in plasma, granulocytes, and sputum. The antibodydetects as little as 1 ng of rECP, can be used both in reducing andnonreducing conditions, and does not cross-react with the highlyhomologous eosinophil-derived neurotoxin or other proteins of thepancreatic ribonuclease superfamily.
Suppression of T-cell responsiveness by inducible cAMP early repressor (ICER)
Authors: Bodor Josef , Feigenbaum Lionel , Bodorova Jana , Bare Cathy , Reitz Marvin S , Gress Ronald E 
Published: September 2022

AbstractDepending on the nature of the costimulation of T lymphocytes, expression of regulatory cytokines and chemokines is either susceptibleor resistant to cyclic AMP (cAMP)-mediated inhibition. Our data showthat cAMP-mediated inhibition of endogenously expressed cytokines, which is characteristic for T helper (Th) 1- and Th 2-like phenotypes, correlates with the induction of a potent transcriptional repressor, inducible cAMP early repressor (ICER), in both subsets of T cellsactivated under conditions of suboptimal interleukin-2 (IL-2)expression. Importantly, Th-specific expression of certain chemokinesis also susceptible to cAMP-mediated transcriptional attenuation. Todetermine whether ICER per se, rather than forskolin-mediated elevationof intracellular cAMP, is responsible for the observed inhibitoryeffect, we generated transgenic mice expressing ICER under the controlof a lymphocyte-specific lck promoter. On stimulation, transgenic thymocytes overexpressing ICER exhibited reduced levels of IL-2 and interferon (IFN)-γ and failed to express the macrophageinflammatory protein (MIP)-1α and MIP-1β genes. Splenic T cellsfrom ICER-transgenic mice showed a defect in proliferation and lacked amixed lymphocyte reaction response, implying that ICER-mediatedinhibition of cytokine and chemokine expression might play an importantrole in T-cell inactivation.
Gelatinase B functions as regulator and effector in leukocyte biology
Authors: Opdenakker Ghislain , Van den Steen Philippe E , Dubois Bénédicte , Nelissen Inge , Van Coillie Els , Masure Stefan , Proost Paul , Van Damme Jo 
Published: September 2022

AbstractMatrix metalloproteinases (MMPs) form a family of enzymes with major actions in the remodeling of extracellular matrix (ECM) components. Gelatinase B (MMP-9) is the most complex family member in terms of domain structure and regulation of its activity. Gelatinase B activity is under strict control at various levels: transcription of the gene by cytokines and cellular interactions; activation of the pro-enzyme by a cascade of enzymes comprising serine proteases and other MMPs; and regulation by specific tissue inhibitors of MMPs (TIMPs) or by unspecific inhibitors, such as α2-macroglobulin. Thus, remodeling ECM is the result of the local protease load, i.e., the net balance between enzymes and inhibitors. Glycosylation has a limited effect on the net activity of gelatinase B, and in contrast to the all-or-none effect of enzyme activation or inhibition, it results in a higher-level, fine-tuning effect on the ECM catalysis by proteases in mammalian species. Fast degranulation of considerable amounts of intracellularly stored gelatinase B from neutrophils, induced by various types of chemotactic factors, is another level of control of activity. Neutrophils are first-line defense leukocytes and do not produce gelatinase A or TIMP. Thus, neutrophils contrast sharply with mononuclear leukocytes, which produce gelatinase A constitutively, synthesize gelatinase B de novo after adequate triggering, and overproduce TIMP-1. Gelatinase B is also endowed with functions other than cleaving the ECM. It has been shown to generate autoimmune neo-epitopes and to activate pro-IL-1β into active IL-1β. Gelatinase B ablation in the mouse leads to altered bone remodeling and subfertility, results in resistance to several induced inflammatory or autoimmune pathologies, and indicates that the enzyme plays a crucial role in development and angiogenesis. The major human neutrophil chemoattractant, IL-8, stimulates fast degranulation of gelatinase B from neutrophils. Gelatinase B is also found to function as a regulator of neutrophil biology and to truncate IL-8 at the aminoterminus into a tenfold more potent chemokine, resulting in an important positive feedback loop for neutrophil activation and chemotaxis. The CXC chemokines GRO-α, CTAP-III, and PF-4 are degraded by gelatinase B, whereas the CC chemokines MCP-2 and RANTES are not cleaved.
Agonistic and antagonistic activities of chemokines
Authors: Loetscher Pius , Clark-Lewis Ian 
Published: September 2022

AbstractSince the discovery of interleukin-8, about 50 chemokines have been identified and characterized. Originally, they were considered as inducible mediators of inflammation, but in recent years, several chemokines were identified that are expressed constitutively and function in physiological traffic and homing of leukocyte—lymphocytes in particular. All chemokines act via seven-transmembrane domain, G protein-coupled receptors. Eighteen such receptors have been identified so far. Studies on structure-activity relationships indicate that chemokines have two main sites of interaction with their receptors, the flexible NH2-terminal region and the conformationally rigid loop that follows the second cysteine. Chemokines are thought to dock onto receptors by means of the loop region, and this contact is believed to facilitate the binding of the NH2-terminal region that results in receptor activation. These studies have also highlighted the importance of the NH2-terminal region for agonistic and antagonistic activity. Recently, we have shown that some naturally occurring chemokines can function as receptor antagonists. These observations suggest a new mechanism for the regulation of leukocyte recruitment during inflammatory and immune reactions, which are based on the combination of agonistic and antagonistic effects.
Control of chromatin accessibility for V(D)J recombination by interleukin-7
Authors: Huang Jiaqiang , Muegge Kathrin 
Published: September 2022

AbstractIL-7 is a key factor for lymphoid development, and it contributes to V(D)J recombination at multiple loci in immune-receptor genes. IL-7 signal transduction, involving γc and Jak3, is required for successful recombination at the TCR-γ locus. IL-7 signaling controls the initiation phase of V(D)J recombination by controlling access of the V(D)J recombinase to the locus. In the absence of IL-7, the TCR-γ locus is methylated and packaged in a repressed form of chromatin consisting of hypoacetylated histones. IL-7 signaling likely increases the acetylation state of the nucleosomal core histones resulting in an “open” form of chromatin. This opening leads to a higher accessibility for the transcription machinery and increased accessibility of the Rag heterodimer that performs the cleavage of DNA.
Functional classification of interferon-stimulated genes identified using microarrays
Authors: de Veer Michael J , Holko Michelle , Frevel Mathias , Walker Eldon , Der Sandy , Paranjape Jayashree M , Silverman Robert H , Williams Bryan R G 
Published: September 2022

AbstractInterferons (IFNs) are a family of multifunctional cytokines thatactivate transcription of subsets of genes. The gene products inducedby IFNs are responsible for IFN antiviral, antiproliferative, andimmunomodulatory properties. To obtain a more comprehensive list and abetter understanding of the genes regulated by IFNs, we compiled datafrom many experiments, using two different microarray formats. Thecombined data sets identified &gt;300 IFN-stimulated genes (ISGs). Toprovide new insight into IFN-induced cellular phenotypes, we assignedthese ISGs to functional categories. The data are accessible on the World Wide Web at http://www.lerner.ccf.org/labs/williams, including functional categories and individual genes listed in asearchable database. The entries are linked to GenBank and Unigenesequence information and other resources. The goal is to eventuallycompile a comprehensive list of all ISGs. Recognition of the functionsof the ISGs and their specific roles in the biological effects of IFNsis leading to a greater appreciation of the many facets of theseintriguing and essential cytokines. This review focuses on thefunctions of the ISGs identified by analyzing the microarray data andfocuses particularly on new insights into the protein kinaseRNA-regulated (PRKR) protein, which have been made possible with theavailability of PRKR-null mice.
Transient expansion of peptide-specific lymphocytes producing IFN-γ after vaccination with dendritic cells pulsed with MAGE peptides in patients with mage-A1/A3-positive tumors
Authors: Toungouz M , Libin M , Bulté F , Faid L , Lehmann F , Duriau D , Laporte M , Gangji D , Bruyns C , Lambermont M , Goldman M , Velu T 
Published: September 2022

AbstractAssessment of T-cell activation is pivotal for evaluation of cancerimmunotherapy. We initiated a clinical trial in patients with MAGE-A1and/or -A3 tumors using autologous DC pulsed with MAGE peptides aimedat analyzing T-cell-derived, IFN-γ secretion by cytokine flowcytometry and ELISPOT. We also tested whether further KLH additioncould influence this response favorably. Monocyte-derived DC weregenerated from leukapheresis products. They were pulsed with therelevant MAGE peptide(s) alone in group A (n=10 pts) andadditionally with KLH in group B (n=16 pts). A specific buttransient increase in the number of peripheral blood T lymphocytessecreting IFN-γ in response to the vaccine peptide(s) was observed in6/8 patients of group A and in 6/16 patients of group B. We concludethat anti-tumor vaccination using DC pulsed with MAGE peptides inducesa potent but transient anti-MAGE, IFN-γ secretion that is notinfluenced by the additional delivery of a nonspecific, T-cellhelp.
The search for new vaccines against tuberculosis
Authors: Orme Ian M 
Published: September 2022

AbstractThe failure of the BCG vaccine for tuberculosis in large, controlledclinical trials, coupled with the gradual consensus that it is mostlyineffective in preventing adult pulmonary disease in endemic areas, hasled to a concerted effort to develop a new generation of vaccines. Thiswork is ongoing in a variety of areas, including DNA vaccines, subunitvaccines, recombinant vaccines, and auxotrophic vaccines. Several suchcandidates are giving promising results in mouse and guinea pig,aerosol-challenge infection models and should move to clinical trialsin the near future.
Surfactant protein D-coatedKlebsiella pneumoniaestimulates cytokine production in mononuclear phagocytes
Authors: Keisari Yona , Wang Hongbin , Mesika Adi , Matatov Robert , Nissimov Liat , Crouch Erika , Ofek Itzhak 
Published: September 2022

AbstractEncapsulated Klebsiella pneumoniae strains K21a, K10, and K50, all of which contain dimannose sequences in their capsular polysaccharides that are recognized by the mannose receptor of macrophages, stimulated interleukin secretion and cytokine mRNA expression by human monocyte-derived macrophages. By contrast, the corresponding unencapsulated phase variants and the K2 strain, which lack the dimannose sequence, did not. Coating of unencapsulated phase variants of Klebsiella strains with surfactant protein (SP)-D resulted in marked stimulation of cytokine mRNA accumulation. The induction of cytokine mRNA via the mannose receptor occurred only in monocyte-derived macrophages, whereas that caused by SP-D-coated Klebsiella strains occurred in both macrophages and peripheral-blood monocytes.The results suggested that innate immunity against pulmonary pathogens might be mediated by SP-D, which acts as an opsonin to enhance the interaction of macrophages with unencapsulated phase variants originating from the upper respiratory tract, and by macrophage mannose receptors, which recognize encapsulated variants expressing capsular dimannose residues.
Synthetic peptide MMK-1 is a highly specific chemotactic agonist for leukocyte FPRL1
Authors: Hu Jin Yue , Le Yingying , Gong Wanghua , Dunlop Nancy M , Gao Ji Liang , Murphy Philip M , Wang Ji Ming 
Published: September 2022

AbstractHuman phagocytic leukocytes express the seven-transmembraneG-protein-coupled receptors formyl peptide receptor (FPR) and FPR-like1 (FPRL1). MMK-1, a synthetic peptide derived from a random peptidelibrary, is reported to induce calcium mobilization specifically inhuman FPRL1 gene-transfected cells. However, its actions onhuman phagocytic leukocytes remain poorly defined. We found that MMK-1is a potent chemotactic and calcium-mobilizing agonist for humanmonocytes, neutrophils, and FPRL1-transfected human embryonic kidney(HEK) 293 cells but is inactive in cells transfected with FPR. MMK-1also activated HEK 293 cells transfected with FPR2, a mousecounterpart of human FPRL1. Furthermore, MMK-1 increasedpertussis toxin-sensitive production of inflammatory cytokines in humanmonocytes. MMK-1 signaling in human phagocytes was completelydesensitized by a well-defined FPRL1 agonist, suggesting thatFPRL1 is likely a receptor that mediates the action of MMK-1 in primarycells. Since MMK-1 is one of the most potent FPRL1-specific agonistsidentified so far, it can serve as a modulator of the hostdefense and a useful agent for further studying the signaling andfunction of FPRL1.
Unlocking the secrets of cytotoxic granule proteins
Authors: Smyth Mark J , Kelly Janice M , Sutton Vivien R , Davis Joanne E , Browne Kylie A , Sayers Thomas J , Trapani Joseph A 
Published: September 2022

AbstractCytotoxic lymphocytes largely comprise CD8+ cytotoxic T cells and natural killer cells and form the major defense of higher organisms against virus-infected and transformed cells. A key function of cytotoxic lymphocytes is to detect and eliminate potentially harmful cells by inducing them to undergo apoptosis. This is achieved through two principal pathways, both of which require direct but transient contact between the killer cell and its target. The first, involving ligation of TNF receptor-like molecules such as Fas/CD95 by their cognate ligands, results in mobilization of conventional, programmed cell-death pathways centered on activation of pro-apoptotic caspases. This review concentrates on the second pathway, in which the toxic contents of secretory vesicles of the cytotoxic lymphocyte are secreted toward the target cell, and some toxins penetrate into the target cell cytoplasm and nucleus. In addition to invoking a powerful stimulus to caspase activation, this “granule-exocytosis mechanism” provides a variety of additional strategies for overcoming inhibitors of the caspase cascade that may be elaborated by viruses. The key molecular players in this process are the pore-forming protein perforin and a family of granule-bound serine proteases or granzymes. The molecular functions of perforin and granzymes are under intense investigation in many laboratories including our own, and recent advances will be discussed. In addition, this review discusses the evidence pointing to the importance of perforin and granzyme function in pathophysiological situations as diverse as infection with intracellular pathogens, graft versus host disease, susceptibility to transplantable and spontaneous malignancies, lymphoid homeostasis, and the tendency to auto-immune diseases.