Metkar S S, Naresh K N, Redkar A A, Nadkarni J J
Immunology Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai, India.
Cancer Immunol Immunother. 1998 Oct;47(2):104-12. doi: 10.1007/s002620050510.
Modulation of Fas expression and function by CD40 ligation was investigated in the Fas-sensitive human Hodgkin's disease cell line HDLM2. The recombinant human trimeric soluble CD40L (sCD40L) protected this cell line from apoptosis induced by an agonistic Fas antibody at all concentrations tested. sCD40L also protected HDLM2 when added up to 2 h after Fas ligation. Apoptosis induced by a cell-permeable synthetic ceramide could not be prevented by sCD40L. Thus, CD40 ligation is likely to intervene in the early phases of the Fas signal transduction pathway. When CD40 ligation preceded Fas ligation, it rendered the cells refractory to Fas-induced apoptosis. sCD40L-mediated protection could not be attributed to reduction in surface Fas expression, increase in Bcl-2 levels or to increase in the levels of soluble Fas isoforms.
在对Fas敏感的人霍奇金病细胞系HDLM2中,研究了CD40连接对Fas表达和功能的调节作用。重组人三聚体可溶性CD40L(sCD40L)在所有测试浓度下,均可保护该细胞系免受激动性Fas抗体诱导的凋亡。在Fas连接后长达2小时添加sCD40L,也可保护HDLM2。细胞可渗透的合成神经酰胺诱导的凋亡不能被sCD40L阻止。因此,CD40连接可能干预Fas信号转导途径的早期阶段。当CD40连接先于Fas连接时,它使细胞对Fas诱导的凋亡产生抗性。sCD40L介导的保护作用不能归因于表面Fas表达的降低、Bcl-2水平的增加或可溶性Fas异构体水平的增加。