bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term-impaired expression of nuclear factor-κB and IκBα in peripheral blood mononuclear cells of trauma patients
Authors: Adib-Conquy Minou , Asehnoune Karim , Moine Pierre , Cavaillon Jean-Marc 
Published: September 2022

AbstractNuclear factor (NF)-κB expression and dimer characteristics were studied in peripheral blood mononuclear cells (PBMCs) of major-trauma patients and healthy controls. Analysis of PBMCs on days 1, 3, 5, and 10 after trauma revealed that expression of both p65p50 heterodimers and p50p50 homodimers was significantly reduced compared with that in controls. In vitro lipopolysaccharide (LPS) stimulation of PBMCs induced NF-κB translocation. However, throughout the survey, p65p50 activation remained significantly lower in trauma patients than in controls. After LPS stimulation in vitro, the p65p50/p50p50 ratio was significantly lower in PBMCs from trauma patients than from healthy controls. The ex vivo expression of IκBα was higher in PBMCs of controls than of trauma patients. LPS did not induce IκB expression in PBMCs from trauma patients, but strong induction was obtained with staphylococci, suggesting that this defect is not universal and depends on the nature of the activating signal. Although no direct correlation was found between levels of interleukin-10 or transforming growth factor-β and NF-κB, these immunosuppressive cytokines were significantly elevated in trauma patients by 10 days after admission. The long-term low-basal and LPS-induced nuclear translocation of NF-κB recalled long-term immunoparalysis observed in patients with severe inflammatory stress such as trauma.
Dimeric S100A8 in human neutrophils is diminished after phagocytosis
Authors: Kumar Rakesh K , Yang Zheng , Bilson Susan , Thliveris Soula , Cooke Bridget E , Geczy Carolyn L 
Published: September 2022

AbstractS100A8 is a major cytoplasmic protein of neutrophils andmonocytes/macrophages and has been associated with myeloid celldifferentiation and activation. Little is known about its functions ormechanisms of release from neutrophils. We have developed a monoclonalantibody to murine S100A8, which cross-reacts with human S100A8. Thisantibody, which recognizes the homodimeric form of the protein, detectsits expression specifically in human neutrophils and is reactive informalin-fixed, paraffin-embedded tissues. Using this antibody as wellas a commercially available antibody to human S100A8, we show thatphagocytic activation of neutrophils, in vivo in acuteappendicitis and in vitro following phagocytosis ofopsonized zymosan, is characterized by loss of cytoplasmicimmunoreactivity for S100A8. In vitro, phagocytosis isassociated with rapid diminution of immunostaining without loss ofviability. Loss of immunoreactivity for S100A8 may serve as a marker oflocalized neutrophil activation in tissues.
Leukocyte recruitment at sites of tumor: dissonant orchestration
Authors: Carlos T M 
Published: September 2022

AbstractBiopsies of tumors responding to interleukin 2 (IL-2) based immunotherapy have been reported to show a leukocytic infiltration. Clinical responses to IL-2-based immunotherapy, however, are limited, suggesting a failure of leukocyte localization at tumor sites. Leukocyte infiltration at inflammatory sites requires local activation of leukocytes and endothelial cells in a coordinated and defined temporal sequence. There is evidence supporting the theory that infiltration of leukocytes at tumor sites is suboptimal due to a failure of coordination of these localizing events. In this review, factors involved in leukocyte recruitment at sites of inflammation and the coordination of these factors in a successful model of inflammation, i.e., wound healing, are discussed. This example is contrasted with events at tumor sites where alterations in expression of cell adhesion molecules or in the production of activating agents may be present. Additionally, the systemic administration of an activating cytokine such as IL-2 may fail to duplicate events that normally occur within a local environment. These observations may facilitate the design of future immunotherapy trials.
IL-1 and TNF independent pathways mediate ICAM-1/VCAM-1 up-regulation in ischemia reperfusion injury
Authors: Burne Melissa J , Elghandour Asmaa , Haq Mahmud , Saba Sabiha R , Norman James , Condon Thomas , Bennett Frank , Rabb Hamid 
Published: September 2022

AbstractIn vitro studies have suggested that targeting interleukin (IL)-1 and tumor necrosis factor (TNF) can be used to regulate intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and potentially treat kidney inflammation. We therefore evaluated ICAM-1 and VCAM-1 regulation in knockout (KO) mice deficient in both IL-1 receptor 1 (R1) and TNF-R1 during renal ischemia reperfusion injury. ICAM-1 and VCAM-1 mRNA expression was measured with specific murine probes and Northern blotting (n =4/group). Protein expression was measured using immunohistochemistry. Serum creatinine (SCr), tubular histology, and neutrophil infiltration into postischemic kidneys were also quantified. ICAM-1 and VCAM-1 mRNA expression increased in both wild-type (WT) and KO mice at 2, 6, and 24 h. Protein expression of ICAM-1 and VCAM-1 was also increased at 24 h postischemia. SCr levels and tubular necrosis scores were comparable in WT and KO mice at 24 and 48 h. Neutrophil migration in KO mice was decreased at 24 h but comparable to WT at 48 h. These data demonstrate that IL-1 and TNF are not essential for postischemic increases in ICAM-1 and VCAM-1.
IgE-regulated loss, not IgE-regulated synthesis, controls expression of FcɛRI in human basophils
Authors: MacGlashan Donald , Xia Han-Zhang , Schwartz Lawrence B , Gong Jianping 
Published: September 2022

AbstractExpression of the high-affinity receptor on basophils and mast cells is modulated by immunoglobulin E (IgE) antibody. Recent studies have shown that modulation occurs through interaction of IgE with the receptor itself, but the mechanisms underlying this control are not understood. Taking both a theoretical and experimental approach, we examined several competing models that focus on whether there is IgE-regulated loss, IgE-regulated synthesis, or both regulated loss and synthesis of the Fc receptor for IgE (FcɛRI). We report that removing IgE from occupied FcɛRI resulted in an accelerated loss only in the unoccupied receptor, with no loss of occupied receptors and no loss of total receptors when all receptors were occupied. Together with previous studies, these results establish that there was IgE-regulated loss of receptors. An examination of synthetic rates of FcɛRIα using pulse-labeling with 35S-methionine indicated no difference in synthetic rates in the presence or absence of IgE. Similarly, the presence or absence of IgE had no influence on the levels of mRNA for either α, β, or γ subunits of FcɛRI. Using model simulations, we found that regulated-synthesis models could be distinguished from regulated-loss/constant-synthesis models on the basis of the relationship between starting FcɛRI densities and changes in density after culture for 1 week in the absence of IgE. Experimental data from this type of study fit a regulated-loss model that did not include regulation of synthesis. Taken together, these results suggest that IgE regulates cell surface expression of FcɛRI only by regulating the rate that receptor is lost from the cell surface.
Expression of CD94 and NKG2 molecules on human CD4+ T cells in response to CD3-mediated stimulation
Authors: Romero Pilar , Ortega Consuelo , Palma Agustín , Molina Ignacio J , Peña José , Santamaría Manuel 
Published: September 2022

AbstractWe investigated the ability of human peripheral CD4+ cellsto express CD94 and NKG2 molecules as a consequence ofCD3-mediated activation. Using highly purified peripheralCD4+ T cells, we found expression of both CD94 and NKG2A 15days after CD3-mediated stimulation of cells. We also determined byreverse transcriptase-PCR that all gene members of NKG2 family—namely,NKG2A, -C, -D, and -E—are sequentially expressed on CD4+cells. We found that this expression is tightly regulated by cytokines,and we identified transforming growth factor-β1 and interleukin-10 asthe main factors that, on CD3-dependent stimulation, positivelycontribute to the expression of CD94 and NKG2A on CD4+cells. We also investigated the functional role of NKG2A and found thatcoligation of CD3 and NKG2A by specific monoclonal antibodies resultsin significant inhibition of interferon γ and tumor necrosis factorα production by stimulated CD4+ cells. The presence andfunction of these receptors on CD4+ lymphocytes support amore general role for NKG2 molecules, whose functions were originallythought to be confined to cytotoxic cells, in the immune system.
Voltage-dependent and calcium-activated ion channels in the human mast cell line HMC-1
Authors: Duffy S M , Leyland M L , Conley E C , Bradding P 
Published: September 2022

AbstractThe mechanisms underlying the recruitment, differentiation, and sustained activation of mast cells in disease are likely to include modulation of ion channels. Specific Ca2+, K+, and Cl− conductances have been identified in rodent mast cells, but there are no equivalent data on human mast cells. We have used the whole-cell patch-clamp technique to characterize macroscopic ion currents in both the human mast cell line HMC-1 and human skin mast cells (HSMCs) at rest and in HMC-1 after activation with calcium ionophore. HSMCs were electrically silent at rest. In contrast, HMC-1 expressed a strong outwardly rectifying voltage-dependent Cl− conductance characteristic of ClC-4 or ClC-5 and a small inwardly rectifying K+ current not carried by the classical Kir family of K+ channels. Calcium ionophore induced the appearance of outwardly rectifying Ca2+-activated Cl− and K+ currents, while hypotonicity induced another outwardly rectifying conductance typical of ClC-3. Reverse transcription-PCRs confirmed that mRNAs for the voltage-dependent Cl− channels ClC-3 and –5 were expressed. This is the first definitive description of a ClC-4/5-like current in a native leukocyte. We suggest that this current may contribute to the malignant phenotype while the Ca2+-activated K+ and Cl− currents may be involved in cell activation.
Monocyte differentiation in intestine-like macrophage phenotype induced by epithelial cells
Authors: Spöttl T , Hausmann M , Kreutz M , Peuker A , Vogl D , Schölmerich J , Falk W , Andreesen R , Andus T , Herfarth H , Rogler G 
Published: September 2022

AbstractMacrophages in normal colonic mucosa show a specific and distinct phenotype with low expression of the typical monocyte/macrophage surface antigens CD14, CD16, and CD11b and T-cell costimulatory molecules. A method for the in vitro induction of a macrophage phenotype similar to this intestinal phenotype is presented. Multicellular spheroids (MCSs) of intestinal epithelial cell (IEC) and control cell lines were cocultured with elutriated monocytes. Surface antigen expression was analyzed by immunohistochemistry and flow cytometry. Interleukin (IL)-1β mRNA was measured by quantitative PCR. Monocytes adhered and infiltrated the MCSs within 24 h. In the MCSs of all IEC lines, the typical monocyte/macrophage surface antigens CD14, CD16, CD11b, and CD11c, which are detectable after 24 h of coculture by immunohistochemistry and flow cytometry, were down-regulated after 7 days (e.g., for CD14 at 24 h, expression was 86% of CD33+ cells; at day 7, it was 11%). A clear decrease of lipopolysaccharide (LPS)-stimulated IL-1β transcription in monocytes cocultured with IEC MCSs could be observed during the 7-day period. For the first time an intestine-like macrophage-phenotype could be induced in vitro. Interactions with IECs play an essential role during this differentiation, which is of functional relevance, e.g., for LPS-induced cytokine secretion.
Feedback activation of T-cell antigen-presenting cells during interactions with T-cell responders
Authors: Mannie Mark D , Walker Mindi R 
Published: September 2022

AbstractLike many T cells in the myelin basic protein (MBP)-specific T-cell repertoire, CD4− GP2.3H3.16 (3H3) T cells recognize guinea pig MBP as an agonist but recognize autologous rat (R)MBP as a mixed agonist/antagonist. 3H3 T cells do not exhibit proliferative responses to RMBP but nonetheless respond to RMBP by accumulation of T-cell surface I-A/peptide complexes and generation of T-cell antigen-presenting cell (T-APC) activity. This study showed that presentation of RMBP by 3H3 T-APC is long-lived but is lost during interactions with cognate responders or on overt activation of T-APCs. Presentation of RMBP to encephalitogenic T cells resulted in the reciprocal activation of 3H3 T-APCs as evidenced by blastogenesis, proliferation, and induction of interleukin-2R and OX40 markers on 3H3 T-APC. These data indicate that T-APCs, like B-cell APCs, undergo clonal expansion after presentation of a cognate antigen to T-cell responders.
Deleterious effects ofEchinacea purpureaand melatonin on myeloid cells in mouse spleen and bone marrow
Authors: Currier N L , Sicotte M , Miller S C 
Published: September 2022

AbstractThe neurohormone, melatonin, a product of the pineal gland, is a potent immune cell stimulant. Phytochemicals contained in root extracts of the plant species Echinacea purpurea are also potent as immune cell stimulants. Both agents are potent stimulants of T, B, and/or natural killer cells, but little is known of their effect on other hemopoietic cells, specifically granular leukocytes, also participants in a wide variety of disease defense processes. Given their current popularity and availability for amelioration of a) jet lag and sleep disorders (melatonin) and b) virus-mediated respiratory infections (E. purpurea), we investigated the effects of these agents on granular leukocytes and their precursors, myeloid cells. Mice received these agents daily for 7 or 14 days via the diet, thus mimicking human administration, after which spleens and bone marrow were removed and assessed for mature, differentiated granulocytes and their myeloid progenitors. The influence of these agents was directly related to the stage of cell maturity. Administration of both agents together resulted in significantly elevated levels of myeloid progenitor cells in both bone marrow and spleen and significantly reduced levels of mature, functional granulocyte progeny in both organs, suggesting a) increased precursor proliferation, b) antiapoptosis among the progenitors, and/or c) inhibition of precursor maturation—the latter readily explaining the paucity of mature granulocyte progeny. In conclusion, individual administration of either the herbal derivative and melatonin was either without effect (E. purpurea) or even advantageous (melatonin) to cells of this lineage, but when administered together, these agents significantly perturbed myelopoiesis.
Functional HIV CXCR4 coreceptor on human epithelial Langerhans cells and infection by HIV strain X4
Authors: Tchou I , Misery L , Sabido O , Dezutter-Dambuyant C , Bourlet T , Moja P , Hamzeh H , Peguet-Navarro J , Schmitt D , Genin C 
Published: September 2022

AbstractHIV can cross the intact epithelium of genital mucosae via Langerhans cells. Fresh Langerhans cells are known to express CD4 and CCR5. The presence of CXCR4 on the surface of cultured but not freshly isolated Langerhans cells has been described. In the present study, we demonstrate that CXCR4 was expressed by fresh Langerhans cells isolated and purified from epidermis. However, the percentage of Langerhans cells expressing CXCR4 or CCR5 increased during maturation of the cells in culture, especially in the presence of exogenous granulocyte-macrophage colony-stimulating factor. To determine whether CXCR4 was functional, freshly isolated Langerhans cells were infected with HIV LAI, a T-cell-tropic strain, and p24 protein production was measured in culture supernatants. p24 production was observed when infected Langerhans cells were cocultured with SupT1 cells. However, the presence of HIV provirus DNA was evidenced within the infected Langerhans cells by nested PCR. Ultrastructural studies confirmed the formation of syncytia when Langerhans cells were cocultured with SupT1 cells. Preincubation of Langerhans cells with azidothymidine or SDF-1-α, a natural ligand for CXCR4, prevented infection. These data demonstrated that CXCR4 is present on the surface of Langerhans cells freshly isolated from human skin epidermis and that this expression is functional.
Muramyl dipeptide and mononuclear cell supernatant induce Langhans-type cells from human monocytes
Authors: Mizuno Kana , Okamoto Hiroyuki , Horio Takeshi 
Published: September 2022

AbstractMuramyl dipeptide (MDP) in bacterial cell walls reportedly evokes epithelioid cell granulomas. We examined its effects on multinucleated-giant-cell (MGC) formation from monocytes. Supernatant of concanavalin A-stimulated peripheral blood mononuclear cells (conditioned medium) generated MGCs from monocytes. MDP significantly increased the fusion index of Langhans-type MGCs (LGCs) but did not affect total MGCs. N-Acetylmuramyl-l-alanyl-l-isoglutamine, an MDP analogue, had no effect on MGC formation. MGCs were produced by conditioned medium from CD14++/CD16− monocytes. MDP enhanced the LGC fusion index from CD14++/CD16− monocytes. MGCs were not produced from CD14+/CD16+ monocytes or immature dendritic cells induced by granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL) 4 and only weakly produced from macrophage (M)-CSF- or GM-CSF-induced macrophages. Added MDP did not generate MGCs from CD14+/CD16+ monocytes or dendritic cells but enhanced LGC formation from macrophages. Because IFN-γ, IL-3, and GM-CSF reportedly are important in LGC induction, we added anti-IFN-γ, anti-IL-3, or anti-GM-CSF monoclonal antibody (mAb) concomitantly to the monocyte culture treated with conditioned medium alone or plus MDP. Anti-IFN-γ mAb completely abrogated MGC generation, whereas anti-GM-CSF and anti-IL-3 mAbs significantly inhibited LGCs. These findings suggest that CD14++/CD16− monocytes are fused to form LGCs by MDP derived from granulomatous-disease-causing pathogens with inflammatory mediators such as IFN-γ, IL-3, and GM-CSF.
Agonist-dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia
Authors: McManus Linda M , Bloodworth Rebecca C , Prihoda Thomas J , Blodgett Janet L , Pinckard R Neal 
Published: September 2022

AbstractInexplicable controversies with regard to possible functional defects of neutrophilic polymorphonuclear leukocytes (PMNs) in diabetes persist. The purpose of the present study was to elucidate the relative effectiveness of several PMN agonists in stimulating lysosomal-enzyme secretion and leukotriene (LT) B4 production by PMNs isolated from diabetic subjects. Formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) induced significantly less lysosomal-enzyme secretion and LTB4 production in diabetic-subject PMNs than in normal-subject PMNs. It is surprising that PMNs from these same diabetic subjects responded normally after stimulation with A23187, serum-opsonized zymosan, or phorbol myristate acetate. The in vitro responsiveness of PMNs stimulated with fMLP or PAF was inversely correlated with indices of in vivo glycemic control (fasting plasma glucose and glycated-hemoglobin levels). In combination, these results indicate that hyperglycemia is associated with sustained decreases in PMN function but only in response to agonists that initiate stimulus-response coupling via G-protein-coupled receptors. This agonist-selective reduction in PMN responsiveness may contribute to the compromised host defense associated with sustained hyperglycemia in diabetes.
Induction of fibroblast-like cells from CD34+ progenitor cells of the bone marrow in rheumatoid arthritis
Authors: Hirohata Shunsei , Yanagida Tamiko , Nagai Tatsuo , Sawada Tetsuji , Nakamura Hiroshi , Yoshino Shin'ichi , Tomita Tetsuya , Ochi Takahiro 
Published: September 2022

AbstractTo assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA), we examined the capacity of CD34+ cells from bone marrow to generate fibroblast-like type B synoviocytes. CD34+ cells from the bone marrow of 22 RA patients differentiated into cells with fibroblast-like morphology, which expressed prolyl 4-hydroxylase, in the presence of stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor α (TNF-α), much more effectively than CD34+ cells from bone marrow of 15 control subjects (10 patients with osteoarthritis and 5 healthy individuals). The generation of fibroblast-like cells was not at all observed in cultures with SCF, GM-CSF, and interleukin 4 (IL-4) with or without TNF-α. Generation of fibroblast-like cells was correlated with matrix metalloproteinase (MMP)-1 levels in culture supernatants. Thus, MMP-1 levels were significantly higher in TNF-α-stimulated cultures of bone marrow CD34+ cells from patients with RA than in those from the control group. These results indicate that bone marrow CD34+ cells from patients with RA have abnormal capacities to respond to TNF-α and to differentiate into fibroblast-like cells producing MMP-1, suggesting that bone marrow CD34+ progenitor cells might generate type B synoviocytes and thus could play an important role in the pathogenesis of RA.
IL-12 plays a pivotal role in LFA-1-mediated T cell adhesiveness by up-regulation of CCR5 expression
Authors: Mukai Takao , Iwasaki Masayuki , Gao Ping , Tomura Michio , Yashiro-Ohtani Yumi , Ono Shiro , Murai Masako , Matsushima Kouji , Kurimoto Masashi , Kogo Mikihiko , Matsuya Tokuzo , Fujiwara Hiromi , Hamaoka Toshiyuki 
Published: September 2022

AbstractThe chemokine receptor CCR5 has been implicated in the recruitment of T cells to inflammatory sites. However, the regulation of CCR5 induction on T cells and its contribution to T cell adhesiveness are poorly understood. Using a Th1 clone, 2D6, that can be maintained with interleukin (IL)-12 or IL-2 alone (designated 2D6IL-12 or 2D6IL-2, respectively), we investigated how CCR5 is induced on T cells and whether CCR5 is responsible for up-regulating the function of adhesion molecules. 2D6IL-12 grew, forming cell aggregates, in culture containing IL-12. This was due to lymphocyte function-associated antigen (LFA)-1–intercellular adhesion molecule (ICAM)-1 interaction, because 2D6IL-12 expressed both LFA-1 and ICAM-1 and cell aggregation was inhibited by anti-ICAM-1 monoclonal antibody. Despite comparable levels of LFA-1 and ICAM-1 expression, 2D6IL-2 cells did not aggregate in culture with IL-2. It is important that there was a critical difference in CCR5 expression between 2D6IL-12 and 2D6IL-2; the former expressed high levels of CCR5, and the latter expressed only marginal levels. Both types of cells expressed detectable albeit low levels of RANTES (regulated on activation, normal T expressed and secreted) mRNA. Unlike IL-12 or IL-2, IL-18 induced high levels of RANTES mRNA expression without modulating CCR5 expression. Therefore, combined stimulation with IL-12 and IL-18 strikingly up-regulated 2D6 cell aggregation. Notably, LFA-1-mediated aggregation of 2D6IL-12 cells was suppressed by anti-CCR5 antibody. These results indicate that IL-12 plays a critical role in CCR5 expression on Th1 cells and consequently contributes to CCR5-mediated activation of LFA-1 molecules.