Toxic epidermal necrolysis (TEN) is a rare, life-threatening, mucocutaneous drug reaction, which causes extensive epidermal detachment and serious complications involving ocular structures and internal organs. Recently, intravenous immunoglobulin (IVIG) was suggested to be effective in treating TEN through the blockage of Fas receptors which initiate keratinocyte apoptosis. Herein, we tried IVIG teratment (0.6 g/kg/day for 4 consecutive days) for a case of TEN. As a result, the progression of epidermal detachment was interrupted within 2 days and epithelialization was completed in 3 weeks without significant side effects.
Antigens, CD95 ; Apoptosis ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Keratinocytes ; Stevens-Johnson Syndrome*

Toxic epidermal necrolysis (TEN) is a rare, life-threatening, mucocutaneous drug reaction, which causes extensive epidermal detachment and serious complications involving ocular structures and internal organs. Recently, intravenous immunoglobulin (IVIG) was suggested to be effective in treating TEN through the blockage of Fas receptors which initiate keratinocyte apoptosis. Herein, we tried IVIG teratment (0.6 g/kg/day for 4 consecutive days) for a case of TEN. As a result, the progression of epidermal detachment was interrupted within 2 days and epithelialization was completed in 3 weeks without significant side effects.
Antigens, CD95 ; Apoptosis ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Keratinocytes ; Stevens-Johnson Syndrome*

5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that α-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of α-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that α-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated α-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that α-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.
Antigens, CD95 ; Apoptosis* ; Blotting, Western ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; DNA Damage ; Drug Therapy ; Fluorouracil

CD43 (sialophorin, leukosialin) is a heavily sialylated surface protein expressed on most leukocytes and platelets including T cells. Although CD43 antigen is known to have multiple and complex structure, exact function of CD43 in each cell type is not completely understood. Here we evaluated the role of CD43 in Fas (CD95)-induced cell death in human T lymphoblastoid cell line, Jurkat. Crosslinking CD43 antigen by K06 mAb increased the Fas-mediated Jurkat cell apoptosis and the augmentation was inhibited by treatment with caspase inhibitors. Further, CD43 signaling of Jurkat cells induced Fas oligomerization on the cell surfaces implying that CD43 ligation have effects on early stage of Fas-induced T cell death. These also suggest that CD43 might play an important role in contraction of the immune response by promotion of Fas-induced apoptosis in human T cells.
Receptor Aggregation/immunology ; Jurkat Cells ; Humans ; Caspases/metabolism ; Apoptosis/*immunology ; Antigens, Surface/metabolism ; Antigens, CD95/metabolism/*physiology ; Antigens, CD43/metabolism/*physiology ; Antibodies, Monoclonal/metabolism

Neutrophils are also known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. In this study, neutrophils were cultivated in vitro in the presence or absence of compounds modulating their survival in an attempt to characterize the expression profile of the DC markers. Higher MHC-II, CD80, CD86, CD83, and CD40 expression levels were detected on the surface of the cultured neutrophils for 24 h than on the freshly isolated cells. The annexin V-positive cells showed a higher expression level of the DC markers than the annexin V-negative cells. The population of neutrophils double stained with annexin V and the DC markers increased after being incubated with agonistic anti-Fas Ab. LPS, the anti-apoptotic compound, decreased the CD86 and MHC-II expression levels but 50-60% of the DC marker-positive cells were detected in the annexin V-positive cells. In contrast, CD80, CD86, CD83, and HLA-DR mRNA levels increased in the GM-CSF-treated neutrophils but not in the anti-Fas Ab-treated neutrophils. T cell proliferation was inhibited by co-culturing them with anti-Fas Ab- or LPS-treated neutrophils at a high neutrophil:T cell ratio. However, the superantigen-mediated T cell proliferation was increased by the LPS-treated neutrophils but decreased by the anti-Fas Ab-treated neutrophils. There was a lower level of interferon-gamma production in the T cells co-cultured with anti-Fas Ab-treated neutrophils than with the LPS-treated neutrophils. This suggests that apoptotic neutrophils express DC markers on their surface and the differential expression of DC markers might have a detrimental effect on the immune reaction.
Antigen Presentation ; Antigens, CD/biosynthesis ; Antigens, CD95/pharmacology ; Antigens, Differentiation/*biosynthesis ; *Apoptosis ; Cells, Cultured ; Dendritic Cells/*metabolism ; Humans ; Lipopolysaccharides/pharmacology ; Lymphocyte Activation ; Neutrophils/*metabolism/physiology ; T-Lymphocytes/immunology

PURPOSE: One of the major limiting factors in the use of FK506 (Tacrolimus) is nephrotoxicity, but the mechanisms of nephrotoxicity are not fully understood. In order to elucidate the pathogenesis of FK506 tubulotoxicity, we examined mechanisms of cellular injury induced by FK506 in cultured LLC-PK1 renal tubular cell line. METHODS: The 3H-thymidine uptake and flow cytometric analysis of apoptosis following FK506 treatment were evlauated. The changes of the Fas and Bcl-2 protein in FK506-induced renal tubular cell injury were also investigated by Western blotting. RESULTS: FK506 treatment significantly decreased 3H-thymidine uptake (M+/-S.D., 3591.6+/-274.3 cpm/well vs 2217.6+/-79.7 at 1 microgram/mL, p<0.05), in a dose dependent manner upto 50microgram/mL, indicating that DNA damage is a sensitive indicator of FK506- induced nephrotoxicity. The addition of FK506 (50 microgram/mL) for 96 hours also induced a significant increase in the percentage of cells displaying annexin-V binding from 3.9+/-2.2% in control cells to 34.9+/-8.5% in treated cells (P<0.05), indicating early apoptotic cellwith an increase of Bcl-2 protein levels up to 6.2 fold (mean) on Western blot analysis, and the dose-dependent further increase of Bcl-2 protein was observed at a dose above 5microgram/mL. death. This finding was supported by electrophoretic analysis of the DNA extracted from FK506-treatedcells, where a series of bands correspondingto integer multiples of 180 to 200 base pairs was visualized. The treatment with FK506 at a concentration higher than 1 microgram/mL for 96 hours was seen to cause a significant 3.7 (mean) fold elevation in the expression of the 45 kD Fas protein by Western blot analysis. The exposure to FK506 at dose of 5microgram/mL for 96 hours was also associated with an increase of Bcl-2 protein levels up to 6.2 fold (mean) on Western blot analysis, and the dose-dependent further increase of Bcl-2 protein was observed at a dose above 5 microgram/mL. CONCLUSION: FK506 is directly toxic to renal tubular cells with inhibiting DNA synthesis and inducing cell death in the form of apoptosis. The changes of Fas antigen system and Bcl-2 protein may play roles in mediating FK506-induced apoptosis of renal tubular cells.
Antigens, CD95 ; Apoptosis* ; Base Pairing ; Blotting, Western ; Cell Death ; Cell Line ; DNA ; DNA Damage ; Epithelial Cells* ; Negotiating ; Tacrolimus*

It is known that CD95 (APO-1/Fas) is expressed on the cell surface, and apoptotic cell death can be induced by the CD95 ligation in the cultured, proliferating human retinal pigment epithelial (RPE) cells. However, little is known about CD95 on the non-proliferating RPE cells. In this study, human RPE cells were cultured up to 4 weeks after they reached the confluence, to simulate the non-proliferating RPE cells in situ. There was no significant difference in CD95 expression on the cell surface between the predominantly proliferating, preconfluent cells and predominantly non-proliferating, postconfluent cells in flow cytometric assays. However, unlike proliferating cells, no cellular death occurred in the predominantly non-proliferating cells after the treatment of agonistic anti-CD95 antibody with cycloheximide, pretreated with interferon-gamma. Our results suggest that the CD95/CD95L system probably plays a physiologic role in vivo to remove the abnormal, proliferating RPE cells, and factors other than the surface expression of CD95 may determine the sensitivity to the CD95 signals.
Antigens, CD95/*pharmacology ; Apoptosis/*physiology ; Cells, Cultured ; Human ; Pigment Epithelium of Eye/cytology/*drug effects/*physiology ; Sensitivity and Specificity

Toxic epidermal necrolysis(TEN) is the most dramatic, life-threatening cutaneous drug reaction. TEN is characterized by extensive detachment of the epidermis undergoing full-thickness necrosis. The pathogenetic pathway and specific treatments of TEN have not yet been identified. Recently, several reports suggested that apoptosis in TEN is promoted by proteins such as Fas antigen and high dose intravenous immunoglobulin(IVIG) inhibits Fas-mediated cell death by blocking the Fas receptor. We report a case of TEN in a 26-year-old woman who had been treated with prednisolone due to iritis. She was treated with high dose IVIG(0.4g/Kg/day for 4 days one day and 0.7g/Kg/day for consecutive). In our case, the progression of skin lesion was interrupted after IVIG infusion and favorable vital outcome was achieved with mild adverse effects.
Adult ; Antigens, CD95 ; Apoptosis ; Cell Death ; Epidermis ; Female ; Humans ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Iritis ; Necrosis ; Prednisolone ; Skin ; Stevens-Johnson Syndrome*

Toxic epidermal necrolysis(TEN) is the most dramatic, life-threatening cutaneous drug reaction. TEN is characterized by extensive detachment of the epidermis undergoing full-thickness necrosis. The pathogenetic pathway and specific treatments of TEN have not yet been identified. Recently, several reports suggested that apoptosis in TEN is promoted by proteins such as Fas antigen and high dose intravenous immunoglobulin(IVIG) inhibits Fas-mediated cell death by blocking the Fas receptor. We report a case of TEN in a 26-year-old woman who had been treated with prednisolone due to iritis. She was treated with high dose IVIG(0.4g/Kg/day for 4 days one day and 0.7g/Kg/day for consecutive). In our case, the progression of skin lesion was interrupted after IVIG infusion and favorable vital outcome was achieved with mild adverse effects.
Adult ; Antigens, CD95 ; Apoptosis ; Cell Death ; Epidermis ; Female ; Humans ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Iritis ; Necrosis ; Prednisolone ; Skin ; Stevens-Johnson Syndrome*

BACKGROUND AND OBJECTIVES: Fas and Fas ligand (Fas-L) interactions mediate apoptosis of eosinophils. It is possible that reduction of Fas/Fas-L or Fas-L expression on eosinophils could induce the eosinophilia seen in Samter's triad. The purpose of this study was to analyse the release of LT and Fas/Fas-L expression pattern following exposure to varying concentrations of aspirin in aspirin sensitive nasal polyp (ASP) and non-aspirin sensitive nasal polyp (NASP) patients. MATERIALS AND METHODS: Twenty NASP patients and 16 ASP patients were recruited. Nine healthy subjects served as normal controls. LT levels and Fas/Fas ligand expressions were analysed by ELISA and flow cytometry. RESULTS: Both NASP and ASP patients showed increased release of LT on aspirin exposure in blood and nasal polyps. But ASP patients showed an even greater release of LT on aspirin exposure in blood as compared to NASP patients (p<0.05). LT release from peripheral blood elements do not necessarily coincide with those results obtained from nasal polyps. Eosinophils in ASP patients have significantly decreased Fas expression when compared to NASP patients (p<0.0001). CONCLUSION: These results suggested the role of LT and eosinophils in aspirin intolerance mechanisms in both blood and nasal polyp tissues. The decreased expression of the Fas receptor or defect of Fas/Fas-L interaction could be an important role in pathogenesis of nasal polyp regardless of their association with aspirin sensitivity.
Antigens, CD95 ; Apoptosis ; Aspirin* ; Enzyme-Linked Immunosorbent Assay ; Eosinophilia ; Eosinophils ; Fas Ligand Protein ; Flow Cytometry ; Humans ; Nasal Polyps* ; Viperidae