Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the hypothesis that CD95-L (Fas-L) present on trophoblastic cells plays a part in establishing foeto-placental tolerance by inducing apoptosis of immune defence cells, we cocultured trophoblasts with lymphoid cells and scored the frequency of cell death in these cultures. We prepared human trophoblastic cells from term placentas removed by C-section and placed them in culture for 48 h before introducing the lymphoid cells. We added Jurkat cells, a CD3 + lymphoid cell line, or purified T cells from human blood to the cultured trophoblasts and monitored apoptosis by electron microscopy and flow cytometry after TUNEL or annexin V labelling. The frequency of cell death in the CD3 + cell population was higher when the lymphoid cells were cocultured with trophoblastic cells than when they were cultured alone. This frequency increased with time but was reduced when anti-CD95-L antibodies were added to the culture medium. Cell death was less frequent in the lymphoid cell population when trophoblasts were replaced with human fibroblasts not expressing CD95-L.
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PMID:Lymphoid cell apoptosis induced by trophoblastic cells: a model of active foeto-placental tolerance. 1035 18

To investigate the pathogenesis of aplastic anemia (AA), the apoptosis of CD34+ cells was assayed with annexin V-fluorescein 24 hr and 48 hr after incubation with the serum of normal controls (n = 10), patients with non severe AA (NSAA, n = 13) and severe AA (SAA, n = 10). The CD34+ progenitors from the bone marrow of normal donors contained a significantly greater proportion of apoptotic cells after incubation with serum from SAA patients than that incubated with serum from normal controls and NSAA. Moreover, the percent apoptosis of CD34+ cells after 24 hr incubation with serum from NSAA was slightly higher than that of normal controls. This appears to be related to clinical severity. No significant difference was found in the percent apoptosis of CD34+ cells between incubation for 24 hr and 48 hr with the same serum. To further explore the mechanism of increased apoptosis induced by the serum of AA patients, the expression of the Fas receptor was measured after incubation with serum from the normal controls and AA patients using flow cytometry. After incubation with serum from the AA patients, the Fas receptor was overexpressed, correlating with the increased apoptosis induced by the same serum from AA patients. In addition, the induction of apoptosis and Fas expression on CD34+ cells by serum from the SAA patients was blocked partly by preincubation of the serum with anti-gamma-IFN neutralizing MoAb. These findings suggested that some aberrant components of the serum in the AA patients, which was confirmed partly to be gamma-IFN, can induce CD34+ progenitors apoptosis through the Fas signaling pathway. This may contribute to understanding the decreased number of stem cells characteristic of aplastic anemia.
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PMID:Induction of apoptosis in CD34+ cells by sera from patients with aplastic anemia. 1043 75

Programmed cell death (apoptosis) can be found in normal thyroid tissue and in various diseases affecting the thyroid gland. The Fas/Fas ligand (FasL) system is involved in the induction of apoptosis in human thyrocytes. Cross-linking the Fas receptor with its own ligand or with an antibody capable of oligomerizing with the receptor induces programmed cell death. We investigated the role of Fas-induced apoptosis in primary human thyrocytes in vitro. Cell cultures of normal human thyrocytes were prepared from specimens obtained during surgery for uninodular goiter. Apoptosis was induced by incubation of the cells with a monoclonal IgM anti-Fas antibody. The presence of apoptosis was determined by FACS analysis of FITC-labelled annexin V binding combined with dye exclusion of propidium iodide. We found a significant rate of Fas-induced apoptosis in normal thyrocytes after activation with a monoclonal anti-Fas antibody. TSH was able to inhibit Fas-mediated apoptosis in a dose-dependent manner. This effect was more pronounced when thyrocytes were incubated in the presence of interferon-gamma. Low concentrations of iodine were able to inhibit apoptosis, while high concentrations of iodine increased the rate of Fas-induced apoptosis. Our results show that Fas-mediated apoptosis is inducible in normal human thyrocytes in vitro and is influenced by TSH and iodine. The Fas/FasL system may play an important role in the regulation of cell number within the thyroid gland, and may be involved in the processes leading to goiter in iodine deficiency.
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PMID:Fas-Mediated apoptosis is inhibited by TSH and iodine in moderate concentrations in primary human thyrocytes in vitro. 1043 22

The tumor suppressor gene product p53 can bind to and inhibit the helicase activity of the multisubunit transcription-repair factor TFIIH. We previously reported that p53-mediated apoptosis is attenuated in primary human fibroblasts from individuals with Xeroderma Pigmentosum (XP) that harbor mutations in the TFIIH DNA helicases XPD or XPB. In this study we show that apoptosis is reduced and delayed in three XPD lymphoblastoid cell lines (LCLs), but not in an XPD heterozygote LCL, after exposure to doxorubicin, a DNA-damaging agent and topoisomerase II inhibitor frequently used in cancer therapy. Apoptosis was assessed by quantitation of Annexin V binding to exposed phosphatidylserine residues and by caspase-mediated cleavage of Poly(ADP)Ribose Polymerase (PARP). Apoptosis induced by doxorubicin was suppressed in LCLs retrovirally transduced with the Human Papillomavirus 16 E6 oncoprotein, consistent with the hypothesis that this is a p53-dependent process. PARP cleavage was not delayed in XPD LCLs in response to anti-Fas (CD95) antibody-mediated apoptosis, thus, the defect in the apoptotic pathway in these cells lies upstream of caspase activation. Similar changes in the expression of apoptosis-effector genes, p53, and p53-responsive genes p21Cip1/WAF-1/Sid1 (p21), gadd45, bcl-2 and bax were observed in normal and XPD LCLs after treatment with doxorubicin, indicating that delayed apoptosis was not a consequence of defective transcription of these genes. Thus, our studies provide further support to the hypothesis that XPD and p53 can functionally interact in a p53-mediated apoptotic pathway.
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PMID:Drug-induced apoptosis is delayed and reduced in XPD lymphoblastoid cell lines: possible role of TFIIH in p53-mediated apoptotic cell death. 1046 15

One-month-old male ICR mice were fed a nutritionally adequate, semipurified diet, either ad libitum (AL) or calorie restricted (CR) (40% less food) for 6 months and were killed to obtain spleens. Flow cytometric analysis revealed increased proportions of both CD4+ and CD8+ T cells in CR-fed mice compared to AL-fed mice. The T cell subsets of CR-fed mice were also found to have higher levels of plasma membrane Fas receptor expression. Similarly, Fas-ligand (Fas-L) expression was higher in anti-CD3-stimulated CD4+ and CD8+ T cells. CR-fed mice also had increased numbers of annexin V-positive CD4+ and CD8+ T cells in stimulated splenic lymphocytes suggesting an increased potential for apoptosis. Fas and Fas-L gene expression in splenic lymphocytes, which correlated closely with the observed increased rate of apoptosis, was significantly increased in CR-fed mice compared to AL-fed mice. In conclusion, these results indicate that CR increases the expression of Fas and Fas-L which may contribute to the known beneficial effects of CR such as prolongation of life span by activating chronic physiologically mediated apoptosis.
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PMID:Calorie restriction increases Fas/Fas-ligand expression and apoptosis in murine splenic lymphocytes. 1048 Oct 71

Lupus specific autoantigens are exposed on apoptotic cells. The increased number of apoptotic lymphocytes reported in systemic lupus erythematosus (SLE) may be attributable to abnormalities of lymphocyte Fas expression or serum soluble Fas. In the present study we analysed the count of circulating apoptotic lymphocytes in SLE patients (n=50), by flow cytometry using Annexin V, compared to rheumatoid arthritis patients (RA, n=20), inflammatory bowel disease patients (IBD, n=20) and normal controls (n=20). Lymphocyte Fas expression and serum soluble Fas were measured and related to numbers of apoptotic lymphocytes. The percentage of apoptotic lymphocytes, determined by Annexin V binding, was significantly increased in peripheral blood of SLE patients (median=4.2%) compared with normal healthy donors (median=1.1%) and IBD patients (median=2. 0%) but not RA (median=3.9%). SLE lymphocyte Fas expression was not significantly different from RA or IBD patients. Serum soluble Fas in SLE patients correlated positively with apoptotic lymphocytes and antibodies to double stranded DNA. This study suggests that increased apoptotic lymphocytes and increased lymphocyte Fas expression may not be specific to SLE. Serum soluble Fas may have a role in the regulation of lymphocyte apoptosis in SLE.
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PMID:Lymphocyte apoptosis in systemic lupus erythematosus: relationships with Fas expression, serum soluble Fas and disease activity. 1048 27

We attempted apoptotic cell death induction of T cells infected with human T lymphotropic virus type I (HTLV-I) which induces HTLV-I-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia. T cells acutely infected and expressing HTLV-Igag Ags were killed by cross-linking their TCR with anti-CD3 mAb. Cells in apoptotic process were found by staining with annexin V. The apoptosis was not affected by costimulation through CD28 molecules and was resistant to ligation of Fas molecules. Whereas the virus-infected T cells expressed higher levels of HLA-DR, CD25, CD80, and CD86 Ags than apoptosis-resistant PHA-blasts, the T cell apoptosis was enhanced by addition of exogenous IL-2. Furthermore, in this apoptosis, monocytes played an important role because T cells infected in the absence of monocytes were resistant to the death signals. The apoptosis-sensitive T cells responded to TCR signaling more strongly by proliferating than those apoptosis-resistant cells. Monocytes weakly affected the expression levels of viral Ags on T cells. However, HTLV-I-infected monocytes primed T cells to die by subsequent TCR signaling. T cells primed with the monocytes, subsequently infected in the absence of monocytes, were killed by TCR signaling. These observations suggest that primed and infected T cells could be killed by activation-induced cell death.
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PMID:Monocyte-driven activation-induced apoptotic cell death of human T-lymphotropic virus type I-infected T cells. 1049 Sep 92

Interferon alpha (IFN-alpha) plays a prominent role in the therapy of a variety of diseases. The Fas/FasL system is crucial for the cytotoxic function and the peripheral elimination of activated T lymphocytes (ATC) by a mechanism referred to as activation-induced cell death (AICD). Recent studies suggest a link between IFN-alpha, the 2', 5'- oligoadenylate system and apoptosis. We therefore asked whether IFN-alpha is able to regulate the Fas/FasL pathway and thereby affects AICD. Peripheral blood mononuclear cells (PBMC), purified T cells and ATC of healthy volunteers were stimulated with various agents and the influence of IFN-alpha on Fas/FasL was assessed by mRNA and protein studies. The proportion of ATC undergoing AICD or anti-Fas-induced apoptosis was determined by FITC-annexin V staining and propidium iodide uptake. IFN-alpha upregulated mRNA expression of Fas and FasL in activated PBMC. Furthermore the concentration of the soluble form of FasL (sFasL) was increased in PBMC and T cells co-stimulated with IFN-alpha and various agents, whereas Fas surface expression was enhanced by IFN-alpha alone. IFN-alpha enhanced apoptosis induced by anti-Fas antibody and augmented AICD via the Fas/FasL pathway. IFN-alpha-regulated AICD may contribute to lymphopenia observed during IFN-alpha therapy. Our data further support that IFN-alpha is a multifunctional cytokine with profound effects on the immune cascades.
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PMID:Interferon alpha augments activation-induced T cell death by upregulation of Fas (CD95/APO-1) and Fas ligand expression. 1052 11

Recovery from radiation-induced (RI) bone marrow aplasia depends on appropriate cytokine support. The early effects of exogenous cytokines at the hematopoietic stem and progenitor cell (HSPC) level following irradiation are still largely unknown, especially those of survival factors such as stem cell factor (SCF) and Flt-3 ligand (FL). This study was aimed at A) clarifying Fas/Fas-Ligand (Fas-L) implication in RI apoptosis of CD34+ cells and B) assessing the capacity of a combination of cytokines to mitigate RI apoptosis in HSPCs in vitro. We showed that most of in vitro gamma-irradiated CD34+ HSPCs incubated in a medium devoid of cytokines underwent progressive apoptosis-related changes from 6 h (i.e., decreased CD34 antigen expression, Annexin V binding); then Fas/Fas-L coexpression occurred from 10 h on. A strong DNA fragmentation, as assessed by TUNEL assay and propidium iodide staining, was observed at 24 h. Within a 2.5- to 6-Gy dose range, the RI apoptotic process finally led to 97% CD34+ cell death within 48 h with a complete loss of functionality. Unirradiated cells incubated in the same conditions displayed a significantly reduced apoptotic pattern. The early addition of a combination of SCF, FL, thrombopoietin, and interleukin 3 (4F) after cell irradiation prevented 15% (2.5 Gy) and 12% (4 Gy) of HSPCs, respectively, from RI apoptosis, whereas these cytokines used as single factors were inefficient. Furthermore, irradiated HSPCs (2.5 Gy) incubated with 4F in a serum-free culture system for seven days proliferated, giving rise to an increase in the number of total cells (x5.6-fold) and CD34+ cells (x4.2-fold) and to megakaryocytic and granulomonocytic precursors. These results show that the prevention of apoptosis in in vitro irradiated HSPCs depends on an early combination cytokine support. These data suggest that the early therapeutic administration of anti-apoptotic cytokines may be critical for preserving functional HSPCs from in vivo radiation damage.
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PMID:The reduction of in vitro radiation-induced Fas-related apoptosis in CD34+ progenitor cells by SCF, FLT-3 ligand, TPO, and IL-3 in combination resulted in CD34+ cell proliferation and differentiation. 1052 62

We compared apoptosis in eosinophils from bronchoalveolar lavage (BAL-Eos) with that in eosinophils from peripheral blood (PB-Eos) of 4 patients with chronic eosinophilic pneumonia (CEP). The survival rate of the BAL-Eos on the 3rd day of the culture was significantly higher than that of the PB-Eos (39.1 vs. 1.3%). The percentage of apoptotic cells in the PB-Eos after a 24-hour incubation was higher than that in the BAL-Eos (21.7 vs. 10.6%) according to an analysis with annexin V. We further found that ECF-PI9, an eosinophil chemotactic factor (ECF) derived from an established T cell line (STO-2), significantly suppressed the apoptosis of both PB-Eos and BAL-Eos and prolonged their survival. The expression of Fas on PB-Eos was significantly suppressed by ECF-PI9 (18.5 to 7.37%, p < 0. 05), whereas ECF-PI9 failed to suppress the Fas expression on BAL-Eos (3.3 to 3.6%). In addition, an ECF with similar physicochemical properties and biological functions was isolated from the BAL fluid of patients with CEP. These data demonstrate differences between PB-Eos and BAL-Eos, and indicate that ECF-PI9 is involved in the pathogenesis of CEP.
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PMID:Difference in apoptotic function between eosinophils from peripheral blood and bronchoalveolar lavage in chronic eosinophilic pneumonia. 1052 13


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