bluuebunny/crossref_metadata_2025_split huggingface dataset:
T and B cell immune response to a 55‐kDa endothelial cell‐derived antigen in severe asthma
Authors: Lassalle Philippe , Delneste Yves , Gosset Philippe , Gras‐Masse HÉLÈNe , Wallaert Benoit , Tonnel André‐Bernard 
Published: March 2007

AbstractCurrent concepts on the pathogenesis of chronic asthma emphasize the role of several inflammatory cell populations and their respective mediators that interact in a complex network. However, beside inflammatory cells, lymphocytes are also present in asthmatic airways. Although little is known about their involvement in asthma, it has been suggested that lymphocytes may participate in the development of chronic inflammation either through lymphokine secretion or through antibody production. In this study, we describe circulating IgG autoantibodies, directed against a common 55‐kDa antigen shared by platelets and cultured endothelial cells, and found in 34 out of 97 asthmatic patients. Among epidemiological, clinical and biological characteristics of these asthmatic patients, the anti‐55‐kDa antigen antibodies are mainly restricted to patients with negative cutaneous prick tests (p = 0.0014), and corticosteroid‐dependent asthma (p = 0.0036). These antibodies were also detected in a few patients with autoimmune disorders like systemic lupus erythematosus (3/30) or rheumatoid arthritis (2/36). Both platelet and endothelial cell antigens were cross‐reactive, had an isoelectric point between 8.0 and 9.0, were unsensitive to reducing agents such as 2‐mercaptoethanol. and were not present on either platelet or endothelial cell surface, as determined by immunostaining assay. [3H] Thymidine incorporation assay with peripheral blood mononuclear cells from patients in the presence or in the absence of 55‐kDa antigen, purified from nitrocellulose sheets demonstrated a specific incorporation in 6 out of 13 patients with circulating anti‐55‐kDa antigen antibodies, with index values ranging from 12 to 3. Such a T cell reactivity has also been observed in 3 out to 17 patients without detectable serum anti‐55‐kDa antigen antibodies. Moreover, a significant correlation was found between index values of antigen‐specific T cell reactivity and the forced expiratory volume in one second (r = 0.544, p = 0.003). Our data indicate that the detection of such antibodies allows to distinguish a subgroup of asthmatics in terms of severity and to suggest a relationship between clinical severity and T and B cell autoreactivity to the 55‐kDa platelet/endothelial cell antigen.
Increased and highly stable levels of functional soluble interleukin‐6 receptor in sera of patients with monoclonal gammopathy
Authors: Gaillard Jean‐Philippe , Bataille Régis , Brailly Hervé , Zuber Caroline , Yasukawa Kiyoshi , Attal Michel , Maruo Naoko , Taga Tetsuya , Kishimoto Tadamitsu , Klein Bernard 
Published: March 2007

AbstractSoluble human interleukin‐6 receptor (sIL‐6R) was measured in the serum of 30 healthy individuals, 32 individuals with monoclonal gammopathy of undetermined significance (MGUS), 20 patients with early multiple myeloma (MM) and 54 patients with overt MM. The serum activity recognized by an immunoradiometric assay was determined to be sIL‐6R, because of its binding capacity to IL‐6 and its molecular mass of 55 kDa.All sera of healthy individuals contained sIL‐6R (mean value: 89 ng/ml, range 17‐300 ng/ml). Serum sIL‐6R levels were increased by 51% in patients with MGUS (mean value: 135 ng/ml, p<0.005), by 44% in patients with early myeloma (mean value: 128 ng/ml, p<0.001) and by 116 % in patients with overt MM (mean value: 193 ng/ml, p<0.001). In patients with MM, a complete lack of correlation (p>0.7) was found between serum sIL‐6R levels and other previously recognized prognostic factors in this disease, particularly serum IL‐6 levels and those factors related to tumor cell mass. The independence of serum sIL‐6R levels on tumor cell mass was directly demonstrated by studying four patients with MM treated with autologous bone marrow transplantation for periods of between 320 and 760 days. These levels were found to be remarkably stable and constant, independent of whether patients relapsed or achieved complete remission. Finally, physiological concentrations of sIL‐6R were found to increase by tenfold the sensitivity of human myeloma cell lines to IL‐6. These observations suggest a high control of the sIL‐6R level in vivo, and, possibly, an important functional role of this circulating protein in patients with monoclonal gammopathies.
Tumor necrosis factor induces enhanced responses to platelet‐activating factor and differentiation in human monocytic Mono Mac 6 cells
Authors: Webera Christian , Aepfelbacher Martin , Haag Heinrich , Ziegler‐Heitbrock H. W. Liims , Weber Peter C. 
Published: March 2007

AbstractHuman Mono Mac 6 cells exhibit characterstics of mature blood monocytes. Treatment of these cells with human recombinant human tumor necrosis factor (TNF)resulted in an increase in phagocytosis and phorbol myristate acetate stimulated superoxide anion production at 12 h and growth retardation occurring at 24 h. Moreover, TNF induced a moderate increase of CD14 surface antigen expression, used as a phenotypic marker of monocyte/macrophage differentiation. Platelet‐activating factor (PAF) stimulated a rapid rise in cytosolic free Ca++ ([Ca++]j) of 308 & 93 nM inTNF‐treated cells compared to untreated cells (33 ± 8 nM, n = 4). The effect of TNF was dose and time dependent, evident after 12 h and maximal at 48 h. The enhanced PAF‐induced [Ca++]i rise was inhibited by the PAF receptor antagonist L‐659,989 and EGTA, indicating receptor‐dependent Ca++ influx. Furthermore, L‐659,989 and PAF inhibited specific 3H‐labeled PAF binding inTNF‐treated, but not in untreated cells. Consistently, PAF stimulated arachidonic acid release only in TNF‐treated cells. Preincubation of cells with anti‐TNF monoclonal antibodies abolished TNF‐induced effects, but failed to block lipopolysaccharide (LPS) effects. Distinct mechanisms of action by LPS were reflected by the different ability to induce surface antigen expression. In conclusion, the enhancement of PAF responses by TNF, associated with functional characteristics of differentiation in Mono Mac 6 cells, may represent a specific mechanism of cooperative interaction between PAF and TNF in inflammation, sepsis, immunoregulation and atherogenesis.
Distinct patterns of early response gene expression and proliferation in mouse mast cells stimulated by stem cell factor, interleukin‐3, or IgE and antigen
Authors: Tsai Mindy , Tam See‐Ying , Galli Stephen J. 
Published: March 2007

AbstractStem cell factor (SCF) is encoded at the Sl locus of the mouse and is the ligand for the c‐kit receptor. Recombinant rat SCF164 (rrSCF164) induces proliferation and promotes maturation of mouse mast cells in vitro and in vivo and can also induce c‐kit receptor‐dependent mouse mast cell degranulation. We now report that in both quiescent and non‐quiescent mouse bone marrow‐derived cultured mast cells (BMCMC) rrSCF164 induces increased mRNA levels for the “early response genes” c‐fos, c‐jun and junB but has only slight effects on the expression of junD.Recombinant mouse interleukin‐3 (IL‐3) also promotes proliferation of both quiescent and non‐quiescent BMCMC. However, IL‐3 induces increased expression of c‐fos and juriB only in quiescent BMCMC. Cross‐linking of Fee receptor type I (FcϵRI) on BMCMC by IgE and specific antigen induces a pattern of early gene expression very similar to that induced by rrSCF164. However, BMCMC stimulated through the FcϵRI did not proliferate and, in comparison to control BMCMC, exhibited significantly decreased proliferation in response to rrSCF164 or IL‐3. These results indicate that stimulation of BMCMC proliferation by IL‐3 or rrSCF164 induces distinct patterns of early response gene expression and suggest that the proliferative effects of these growth factors may be mediated through distinct signal transduction pathways. Our data also point to previously unappreciated similarities between the effects of signaling through the c‐kit receptor or the FcϵRI on mast cell expression of fos and jun genes.
In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants
Authors: Nussler Andreas K. , Rénia Laurent , Pasquetto Valerie , Miltgen Francois , Matile Hughes , Mazier Dominique 
Published: March 2007

AbstractThe mechanisms responsible for malarial immunity induced by repetitive injections of X‐irradiated sporozoites have not been fully established. We demonstrate here that a single injection of irradiated sporozoites induced, as soon as 24 h after, a non‐permissive state to hepatocyte reinfection with sporozoites in vitro. The same effect was observed when malarial blood forms, irradiated promastigotes of Leishmania infantum, adjuvants (muramyl dipeptide, poly acidylic uridylic) or interferon‐γ was injected. Activation of the nitric oxide (NO) pathway in the hepatocyte by these factors was found to be responsible for hepatocyte refractory status. Additionally, this metabolic pathway is involved in protection given by repeated injections of irradiated sporozoites since protection could be reversed by treating mice at the time of sporozoite challenge with a competitive inhibitor (NG‐monomethyl‐L‐arginine) of the NO pathway. These results suggest that, in view of an antisporozoite vaccine, further studies are needed to find out how to activate specifically a long‐lasting nonspecific immune response.
Streptavidin blocks immune reactions mediated by fibronectin‐VLA‐5 recognition through an Arg‐Gly‐Asp mimicking site
Authors: Alon Ronen , Hershkoviz Rami , Bayer Edward A. , Wilchek Meir , Lider Ofer 
Published: March 2007

AbstractStreptavidin is a biotin‐binding analogue of egg‐white avidin which is secreted by the bacterium Streptomyces avidinii. We have recently reported that streptavidin contains an Arg‐Tyr‐Asp‐Ser (RYDS) sequence which exhibits structural homology to the Arg‐Gly‐Asp‐Ser (RGDS) cell adhesion domain of fibronectin and other matrix‐associated glycoproteins. Competition studies with RGD peptides indicated that streptavidin binds to cells via this site and that the binding is independent of biotin recognition. Since the RGD‐containing peptide has been shown to play a key role in integrin‐mediated cell adhesion, we assumed that streptavidin may utilize the RYDS site to bind to immune cells and thereby abrogate their adhesion‐dependent functions. We now report that streptavidin modulates several atrix‐dependent interactions of immune cells. In this context, immobilized streptavidin was found to support activated human CD4+ T cell adhesion in an RGD‐specific, α5β1 dependent manner. In addition, soluble streptavidin (the commercially available or biotin‐blocked forms) inhibited T cell adhesion to fibronectin and interfered with its co‐stimulatory effect on tumor necrosis factor‐a secretion by co‐cultures of CD4+ T cells and macrophages. These results suggest that streptavidin is a novel example of a bacterial protein which utilizes RGD mimicry to interfere with integrin‐mediated immune responses.
In situ analyses of in ovo graft‐vs.‐host reaction induced by thymic nurse cell lymphocytes
Authors: Rieker Theresa , Penninger Josef , Hala Karel , Cooper Max D. , Wick Georg 
Published: March 2007

AbstractIn both mammalian and avian systems, thymic nurse cells (TNC) have been shown to harbor a heterogeneous population of T lymphocytes (TNC‐L) some of which exhibit a postselectional phenotype. By tranplanting micromanipulated single chicken TNC onto the chorionallantoic membrane (CAM) of major histocompatibility complex (MHC)‐disparate embryos, an experimental system which allows for the detection of lymphocytes with graft‐vs.‐host (GVH) reactivity, we demonstrate here that TNC enclose lymphocytes that can develop into both CD4+ single‐positive (sp) and CD8+ sp, T cell receptor (TcR)αβ+, or TcRγδ+ cells. This finding was additionally confirmed by serial transfer of primary expanded alloreactive T cells onto the CAM of secondary hosts. All donor TNC‐L expressed MHC class II molecules and the interleukin‐2 receptor a chain in primary and secondary GVH reactions. Furthermore, we observed selective accumulation of CD8+ and TcRγδ+ host lymphocytes in the CAM upon the induction of a local GVH reaction, most probably as a consequence of the pathological alteration of the epithelium.
A subset of anti‐CD21 antibodies promote the rescue of germinal center B cells from apoptosis
Authors: Bonnefoy Jean‐Yves , Henchoz Sybille , Hardie Deborah , Holder Michelle J. , Gordon John 
Published: March 2007

AbstractGerminal center cells (GCC) are programmed to die by apoptosis unless they receive a positive signal for rescue. The primary signal in vivo is believed to be dependent on interaction with antigen held as immune complexes on follicular dendritic cells (FDC), a subset of which express large amounts of CD23, a low‐affinity receptor for IgE. Recombinant soluble CD23 (sCD23) and interleu‐kin‐1 have been found to potentiate the survival of GCC in vitro. Recently, CD23 was shown to interact specifically with a ligand other than IgE, namely CD21 (CR2/Epstein‐Barr virus receptor). In the present study, we show that a subset of anti‐CD21 monoclonal antibodies behave similarly to soluble CD23 in their effect on GCC inasmuch as they: (i) diminish the occurrence of apoptosis; (ii) promote a plasmacytoid appearance in rescued cells; (in) up‐regulate expression of the Bcl‐2 proto‐oncogene. These findings indicate that FDC‐derived CD23 exerts its effect on GCC via CD21.
Interleukin 6 is not required for antigen‐specific antibody responses by human B cells
Authors: Costelloe Katherine E. , Smith Susan H. , Callard Robin E. 
Published: March 2007

AbstractInterleukin‐6 (IL‐6) is a late‐acting differentiation factor for human B cells activated by polyclonal mitogens such as pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I, but its role in specific antibody responses has not been established. We show here that IL‐6 has no consistent effect on specific antibody responses by tonsillar mononuclear cells (TMC) stimulated with influenza virus. A blocking IL‐6 antibody also had no effect on antibody production, suggesting that endogenous IL‐6 production was not required. In control experiments, this antibody inhibited PWM‐stimulated immunoglobulin secretion and proliferation of the IL‐6‐dependent B cell line B9. A requirement for IL‐6 in responses of unfractionated TMC may have been disguised by the presence of Tcells. To overcome this problem, we investigated the effect of IL‐6 on specific antibody production by T‐depleted B cells stimulated with antigen in the presence of IL‐2, which is a Tcell replacing factor (TRF) for human B cells. Specific antibody production was restored by IL‐2, but not IL‐6. Neither IL‐6 nor anti‐IL‐6 antibody had any consistent effect on specific antibody production by purified B cells stimulated with antigen and TRF. These experiments show that IL‐6 does not have a significant role in antigen (influenza virus)‐specific antibody responses by human B lymphocytes.
Eosinophils infiltrating interleukin‐5 gene‐transfected tumors do not suppress tumor growth
Authors: Krüger‐Krasagakes Sabine , Li Weiqun , Richter GÜNther , Diamantstein Tibor , Blankenstein Thomas 
Published: March 2007

AbstractTumor‐associated eosinophils have been observed in human tumors and in experimental tumor models, but their function is poorly understood. To study the role of eosinophils during tumor growth, the plasmacytoma J558L and the mammary adenocarcinoma TS/A were transfected with an expression vector encoding the murine gene for interleukin‐5 (IL‐5), a cytokine inducing proliferation and activation of eosinophils. Injection of parental cells, mock‐transfectants and IL‐5‐producing cells into syngeneic mice showed that local IL‐5 secretion induced rapid tumor infiltration by eosinophils, as evidenced by immunohistochemical staining, but nevertheless did not alter the tumor growth kinetics of IL‐5 transfectants. Therefore, the mere presence of IL‐5 and eosinophils was not sufficient to induce a protective host immune response.
Interleukin‐4 and interleukin‐10 inhibit nitric oxide‐dependent macrophage killing of Candida albicans
Authors: Cenci Elio , Romani Luigina , Mencacci Antonella , Spaccapelo Roberta , Schiaffella Enrico , Puccetti Paolo , Bistoni Francesco 
Published: March 2007

AbstractMouse peritoneal and splenic macrophages treated with interferon‐γ (IFN‐γ) and infected with the yeast Candida albicans expressed high fungicidal activity in vitro that correlated with increased nitrite concentrations in culture supernatants. Both effects were reduced by an inhibitor of nitric oxide (NO) synthesis which, in vivo, impaired the animals' ability to mount a footpad reaction and clear the fungus from infected organs. Because T helper type‐2 (Th2) cytokines in candidiasis are known to limit the expression of protective Th1 functions, we tested the effect of interleukin (IL)‐4 and IL‐10 on candidacidal activity and NO production of IFN‐γ‐activated macrophages. Fungal killing and NO secretion were inhibited, in a dose‐dependent manner, by the two cytokines either separately or in combination. Impaired candidacidal activity was also demonstrable in the presence of monoiodoacetic acid, an inhibitor of phagocytosis. These data demonstrate that NO is involved in macrophage killing of C. albicans and support the notion that regulation of Th1 effector function by IL‐4 and IL‐10 might involve modulation of NO synthesis.
Regulation of CD69 expression on human natural killer cells: differential involvement of protein kinase C and protein tyrosine kinases
Authors: Borrego Francisco , Peña José , Solana Rafael 
Published: March 2007

AbstractHuman peripheral blood natural killer (NK) cells (CD56+, CD16+, CD3ε− lymphocytes) express CD69 after their stimulation by interleukin‐2 (IL‐2) or interferon‐α (IFN‐α). This activation antigen represents a triggering surface molecule in NK cell clones as its stimulation triggers the cytolytic machinery of these cells. However, the mechanisms regulating the expression of CD69 in NK cells are unknown despite the functional relevance of CD69 in NK cell activation. Thus, we have analyzed the role of protein kinase C (PKC) and protein tyrosine kinases (PTK) in the expression of CD69 on purified NK cells activated by IL‐2, IFN‐α, anti FcγRIII (CD16) monoclonal antibodies or by K562 target cells. We found that CD69 is induced on NK cells not only by IL‐2 and IFN‐α but also by activation of the CD 16 pathway, the interaction with NK target cells and the direct activation of PKC by phorbol 12‐myristate 13‐acetate (PMA), indicating that CD69 induction is associated to different NK activation pathways. The treatment with the PKC inhibitor staurosporine abolished the induction of CD69 induced by PMA or K562. However, it did not significantly affect CD69 induction by IL‐2, IFN‐α or CD 16 cross‐linking. This demonstrates that whereas PKC can play a central role in the regulation of CD69 expression in some instances (response to K562 cells or PMA), it does not participate in others (response to IL‐2, IFN‐α or anti CD16 monoclonal antibodies). On the other hand genistein, a competitive inhibitor of PTK enzymes, blocked the expression of CD69 induced by activation of NK cells via IL‐2 or IFN‐α receptors, CD16 and K562 receptor(s), indicating that stimulation of PTK is a common step in the signal transduction events leading to the induction of CD69 antigens after the activation of NK cells via these receptors.
Interferon‐γ and interleukin‐4 reciprocally regulate the production of monocytes/macrophages and neutrophils through a direct effect on committed monopotential bone marrow progenitor cells
Authors: Snoeck Hans‐W. , Lardon Filip , Lenjou Marc , Nys Griet , Van Bockstaele Dirk R. , Peetermans Marc E. 
Published: March 2007

AbstractWe studied the direct effects of interferon‐γ (IFN‐γ) in single cell colony assays of CD34+HLA‐DR++ bone marrow progenitor cells stimulated by either granu‐locyte‐colony‐stimulating factor (G‐CSF), interleukin(IL)‐3, granulocyte/macro‐phage‐colony‐stimulating factor (GM‐CSF), combinations of these CSF or medium conditioned by the 5637 human bladder carcinoma cell line. In this culture system IFN‐γ stimulated monocytic colonies (CFU‐M) no matter which CSF or CSF combination was used to support them and inhibited granulocytic colonies (CFU‐G) if they were generated in the presence of G‐CSF. IL‐4 antagonized the myelopoietic effects of IFN‐γ: the IFN‐γ induced suppression of G‐CSF‐supported CFU‐G, as well as the stimulation of CFU‐M, were reversed by IL‐4. In all cultures, IFN‐γ had a limited, but statistically non‐significant, inhibitory effect on CFU‐GM, which was not affected by the presence of IL‐4. These data show that IFN‐γ and IL‐4 reciprocally regulate the generation of myeloid cells involved in humoral (neutrophils) and cellular (macrophages) immune responses through a direct effect on monopotential myeloid progenitor cells.
Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti‐liver‐kidney microsome type‐1 antibodies (LKM1)
Authors: Yamamoto Ana M. , Cresteil Danièle , Boniface Odile , Clerc François F. , Alvarez Fernando 
Published: March 2007

AbstractAnti‐liver‐kidney microsome type‐1 antibodies (LKM1), present in sera from a group of patients with autoimmune hepatitis, are directed against P450IID6. Previous work, using cDNA constructions spanning most of the P450IID6 protein defined the main immunogenic site between the amino acids (aa), 254–271 and predicted the presence of other putative immunogenic sites in the molecule. Fusion proteins from new cDNA constructions, spanning so‐far‐untested regions between aa 1–125 and 431–522, were not recognized by LKM1‐positive sera. Synthetic peptides, representing sequences from putative immunogenic regions or previously untested regions, allowed a precise definition of four antigenic sites located between peptides 257–269, 321–351, 373–389 and 410–429, which were recognized, respectively, by 14, 8, 1 and 2 out of 15 LKM1‐positive sera tested. The minimal sequence of the main antigenic site (peptide 257‐269) recognized by the autoantibody was established to be WDPAQPPRD (peptide 262–270). In addition, deletion and replacement experiments showed that aa 263 (Asp) was essential for the binding of the autoantibody to peptide 262–270. Analysis of the second most frequently recognized peptide between aa 321–351, was performed using peptides 321–339 and 340–351 in competitive inhibition studies. Complete elimination of antibody binding to peptide 321–351 obtained by absorption of both shorter peptides indicated that peptide 321–351 is a discontinuous antigenic site. LKM1‐positive sera reacting against peptide 321–351 recognized either both the shorter peptides or just one of them preferentially. Results of the present study suggest that the production of LKM1 antibodies is an antigen‐driven, poly‐or oligoclonal B cell response. The identification of antigenic sites will allow: (i) the development of specific diagnostic tests and (ii) further studies on the pathogenic value of LKM1 antibodies in autoimmune hepatitis.