Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and ...Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.展开更多
AIM： To quantify the intraepithelial lymphocytes （IELs） and to document the membrane expression of CD4, CD8, TCRγδ and adhesion and/or activation-associated molecules （CD103, CD28, CD44, CD69, HLA-DR, CD95/ Fas...AIM： To quantify the intraepithelial lymphocytes （IELs） and to document the membrane expression of CD4, CD8, TCRγδ and adhesion and/or activation-associated molecules （CD103, CD28, CD44, CD69, HLA-DR, CD95/ Fas） in the duodenal mucosa of patients with functional dyspepsia （FD） in order to provide arguments for an immunological process in FD. METHODS： Twenty-six FD patients according to Rome Ⅱ criteria （20 were H pylori negative） were studied and compared to 12 healthy adults. IELs were isolated from five duodenal biopsy samples, then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry. RESULTS： Duodenal histological examination was normal. In H pylori negative patients, the number of IELs was not different from that in healthy controls. Median percentage expression of CD4, CD8, or TCRy8 and CD103, CD44, CD28, CD69 on CD3＋ IELs, among the adhesion/activation associated molecules tested, was not different from that in healthy controls. In contrast, the median percentage expression of CD95/ Fas [22 （9-65） vs 45 （19-88）, P = 0.03] and HLADR expressing CD3＋ IELs [4 （0-30） vs 13 （4-42）, P = 0.04] was significantly lower in the H pylori negative FD group than in healthy controls, respectively. The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 （6.7-62.5） vs 10.8 （3-33.3）, P = 0.02] due to a higher number of CD8＋ CD3＋ IELs. CONCLUSION： In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD.展开更多
The cell surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34 + cells freshly isolated from CB displayed ...The cell surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34 + cells freshly isolated from CB displayed low CD95 expression. The combinations of cytokines such as SCF+FL could up regulate the expression of CD95 in vitro culture and tumor necrosis factor α (TNF α) and interon γ (IFN γ) further increased the CD95 expression induced by positive cytokines. The functional status of CD95 mediated apoptosis were analyzed by incubation of CD34 +CB cells in the presence of anti CD95 monoclonal antibodies (McAbs). The effects of anti CD95 McAbs were measured by viable cell counting, flow cytometry, LTIC and CFU C assays. A decrease of viable cells, CFU C and LTIC numbers were observed in the presence of anti CD95 McAbs and TNF α or IFN γ. However, growth factor deprivation or the early acting cytokine such as SCF and FL cross linking to CD95 caused low apoptosis of CD34 + cells. The correlation of increased intracytoplasmic levels of bcl 2 and the presence of CD95 on fresh CB CD34 + cells suggested that bcl 2 might be involved in protecting against CD95 mediated apoptosis of CB CD34 + cells.展开更多
文摘Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.
文摘AIM： To quantify the intraepithelial lymphocytes （IELs） and to document the membrane expression of CD4, CD8, TCRγδ and adhesion and/or activation-associated molecules （CD103, CD28, CD44, CD69, HLA-DR, CD95/ Fas） in the duodenal mucosa of patients with functional dyspepsia （FD） in order to provide arguments for an immunological process in FD. METHODS： Twenty-six FD patients according to Rome Ⅱ criteria （20 were H pylori negative） were studied and compared to 12 healthy adults. IELs were isolated from five duodenal biopsy samples, then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry. RESULTS： Duodenal histological examination was normal. In H pylori negative patients, the number of IELs was not different from that in healthy controls. Median percentage expression of CD4, CD8, or TCRy8 and CD103, CD44, CD28, CD69 on CD3＋ IELs, among the adhesion/activation associated molecules tested, was not different from that in healthy controls. In contrast, the median percentage expression of CD95/ Fas [22 （9-65） vs 45 （19-88）, P = 0.03] and HLADR expressing CD3＋ IELs [4 （0-30） vs 13 （4-42）, P = 0.04] was significantly lower in the H pylori negative FD group than in healthy controls, respectively. The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 （6.7-62.5） vs 10.8 （3-33.3）, P = 0.02] due to a higher number of CD8＋ CD3＋ IELs. CONCLUSION： In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD.
基金This project was supported by a grant from National Na-ture Science Foundation of China (No.3992 80 10 )
文摘The cell surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34 + cells freshly isolated from CB displayed low CD95 expression. The combinations of cytokines such as SCF+FL could up regulate the expression of CD95 in vitro culture and tumor necrosis factor α (TNF α) and interon γ (IFN γ) further increased the CD95 expression induced by positive cytokines. The functional status of CD95 mediated apoptosis were analyzed by incubation of CD34 +CB cells in the presence of anti CD95 monoclonal antibodies (McAbs). The effects of anti CD95 McAbs were measured by viable cell counting, flow cytometry, LTIC and CFU C assays. A decrease of viable cells, CFU C and LTIC numbers were observed in the presence of anti CD95 McAbs and TNF α or IFN γ. However, growth factor deprivation or the early acting cytokine such as SCF and FL cross linking to CD95 caused low apoptosis of CD34 + cells. The correlation of increased intracytoplasmic levels of bcl 2 and the presence of CD95 on fresh CB CD34 + cells suggested that bcl 2 might be involved in protecting against CD95 mediated apoptosis of CB CD34 + cells.
