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Ligand Pathway (ligand + pathway)
Selected AbstractsC-Kit receptor (CD117) expression on myeloblasts and white blood cell counts in acute myeloid leukemiaCYTOMETRY, Issue 1 2004Jolanta Wo Abstract Background The c-Kit receptor is considered to play a crucial role in hematopoiesis. Induction of mobilization of hematopoietic cells in the bone marrow requires cooperative signaling through c-Kit and c-Kit ligand pathway, and these interactions are important in the retention of stem cells within the bone marrow. Therefore, we analyzed c-Kit density on the leukemic myeloblasts of patients with acute myeloid leukemia (AML) in relation to white blood cell count (WBC) in the peripheral blood. Methods Bone marrow aspirates collected from patients with AML and bone marrow aspirates and leukapheresis products after granulocyte colony-stimulating factor blood mobilization from adult volunteers were studied. To determine the level of c-Kit receptor expression, we applied quantitative (relative fluorescence intensity and antibody binding per cell) cytometric methods. Results Our data showed negative correlation between the level of c-Kit expression intensity on myeloblasts and the number of leukocytes in blood of AML patients. The c-Kit receptor density on myeloblasts in patients with low WBC was significantly stronger than that on myeloblasts in patients with high WBC. In the latter patient group, the density c-Kit receptor on myeloblasts was similar to that on CD34+ cells in mobilized peripheral blood. Conclusions The obtained data suggest an involvement of c-Kit receptor in the regulation of leukemic myeloblasts egress to the peripheral blood. © 2004 Wiley-Liss, Inc. [source] Actinobacillus actinomycetemcomitans induces apoptosis of T lymphocytes by the Fas and Fas ligand pathwayMOLECULAR ORAL MICROBIOLOGY, Issue 5 2002A. Nalbant Actinobacillus actinomycetemcomitans expresses a number of toxins capable of inducing apoptotic cell death of T lymphocytes. However, the exact mechanism(s) has not been elucidated. The present study investigated the involvement of the Fas (CD95)-mediated apoptotic pathway in A. actinomycetemcomitans -induced T-cell apoptosis. To that end, peripheral blood mononuclear cells (PBMC) were cultured with or without A. actinomycetemcomitans cell-free culture supernatant (CFCS) for 0,96 h. The cells were then labeled with specific monoclonal antibodies and flow cytometry was performed. Results demonstrated up-regulation of Fas and activation of caspase-3 in T cells in response to A. actinomycetemcomitans CFCS. Monocytes were the only cells analyzed to express Fas ligand (FasL) constitutively, and this was further up-regulated in response to A. actinomycetemcomitans CFCS, while T cells expressed FasL only after this stimulation. Depletion of monocytes prior to stimulation with A. actinomycetemcomitans CFCS led to a marked decline in apoptosis. Blocking of Fas,FasL interactions with anti-Fas monoclonal antibody or Fas:Fc fusion protein lead to a significant decline, but not abolition, of T-cell apoptosis. Nearly all T cells expressed Bcl-2 at the outset of culture, and Bcl-2 expression declined in T cells stimulated with A. actinomycetemcomitans CFCS. Collectively, these data provide evidence for the induction of T-cell apoptosis by A. actinomycetemcomitans via the Fas-mediated pathway, involving caspase-3 and Bcl- 2. Moreover, this apoptotic response was dependent on the presence of monocytes. [source] Interferon-,,dependent inhibition of B cell activation by bone marrow,derived mesenchymal stem cells in a murine model of systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 9 2010Francesca Schena Objective Bone marrow,derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of immune-mediated diseases. This study was undertaken to assess the influence of murine BM-MSCs on the activation of B cells in (NZB × NZW)F1 mice as an animal model of systemic lupus erythematosus (SLE). Methods We evaluated the in vitro effects of BM-MSCs on the proliferation and differentiation to plasma cells of splenic mature B cell subsets, namely follicular and marginal zone B cells isolated from (NZB × NZW)F1 mice. Lupus mice were also treated with BM-MSCs, and serum autoantibodies, proteinuria, histologic changes in the kidney, and survival rates were monitored. Results BM-MSCs inhibited antigen-dependent proliferation and differentiation to plasma cells of follicular and marginal zone B cells in vitro. This inhibitory effect was dependent on interferon-, (IFN,) and was mediated by cell-to-cell contact, involving the programmed death 1 (PD-1)/PD ligand pathway. In vivo treatment with BM-MSCs did not affect the levels of anti,double-stranded DNA antibodies or proteinuria. However, a reduction in glomerular immune complex deposition, lymphocytic infiltration, and glomerular proliferation was observed. Conclusion Our findings indicate that BM-MSCs affect B cell receptor,dependent activation of both follicular and marginal zone B cells from lupus mice. This inhibitory effect is IFN,-dependent and cell contact,dependent. MSCs in vivo do not affect the production of autoantibodies, the level of proteinuria, or the mortality rates. Nonetheless, the significant improvement in histologic findings in the kidney supports the potential role of MSCs in the prevention of glomerular damage. [source] Inducible costimulator ligand regulates bleomycin-induced lung and skin fibrosis in a mouse model independently of the inducible costimulator/inducible costimulator ligand pathwayARTHRITIS & RHEUMATISM, Issue 6 2010Chihiro Tanaka Objective Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin and internal organs, including the lungs. Inducible costimulator (ICOS), which is expressed on activated T cells, and its ligand ICOSL, which is expressed on antigen-presenting cells, have been considered a single receptor,ligand pair. Although the ICOS/ICOSL pathway is known to play various roles in adaptive immunity, its roles in innate immunity and tissue fibrosis remain unknown. Methods We assessed the roles of ICOS and ICOSL in tissue fibrosis by administering bleomycin intratracheally or intradermally into mice deficient in ICOS and/or ICOSL. Tissue fibrosis was evaluated by histologic or biochemical examination. Results ICOS deficiency attenuated the lung and skin fibrosis, whereas ICOSL deficiency aggravated it. Mice deficient in both ICOS and ICOSL exhibited accelerated fibrosis, reflecting a dominant role of ICOSL over ICOS in this model. Interestingly, ICOSL expression on macrophages and B cells derived from bronchoalveolar lavage fluid was significantly elevated in ICOS-deficient mice as compared with wild-type mice during this process. Thus, the levels of ICOSL expression on B cells and macrophages were inversely associated with the severity of tissue fibrosis. Conclusion Our results indicate that ICOSL expression on antigen-presenting cells plays a previously unknown regulatory role during the development of bleomycin-induced tissue fibrosis that is independent of the ICOS/ICOSL pathway. Further studies will be needed to clarify the roles of ICOS and ICOSL in the development of systemic sclerosis. [source] Perforin expression is upregulated in the epidermis of psoriatic lesionsBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004M. Ka, telan Summary Background, There are currently very few data regarding the role of cell-mediated cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK) cells mediate cytotoxicity reactions, mainly by two distinct pathways, the perforin/granzyme and the Fas/Fas ligand pathway. Objectives, To study the expression and distribution of perforin, T- and NK-cell subsets in psoriatic lesional and nonlesional skin. Methods, Skin biopsy specimens from both lesional and nonlesional skin of 11 patients with chronic plaque psoriasis and eight healthy controls were analysed by immunohistochemistry. Results, We found a significant increase in CD4+ and CD8+ cells in psoriatic lesions compared with nonlesional and healthy skin. The expression of CD16+ NK cells was significantly lower in lesions compared with healthy skin. Perforin expression was significantly enhanced in the epidermis of psoriatic lesions. Conclusions, Perforin expression is upregulated in the epidermis of psoriatic lesions, suggesting a potential role for perforin in the creation of the psoriatic plaque. [source] | ||||||||||