|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1998 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Fas ligand (FasL) is a type II membrane protein belonging to the tumor necrosis factor (TNF) family, and induces apoptosis by binding its receptor Fas. A metalloproteinase cleaves the membrane-bound FasL, to produce its soluble form. To determine which forms of FasL, the membrane-bound or soluble form induces apoptosis, we prepared the soluble recombinant FasL and also established transformant cell lines that express non-cleavable membrane-bound FasL. Mouse hepatocytes and human Jurkat cells were killed by the membrane-bound FasL, butnot by soluble FasL, indicating that the membrane-bound form of FasL is the effector molecule, and its cleavage by shedding is to down-regulate the function. TNF is known to be cleaved by TACE (TNF alpha converting enzyme). Biochemical analysis of TACE indicated that TACE should be expressed in the same cells as TNF, and it does not cleave FasL. When the tumor cells expressing FasL are transplanted to peritoneal cavity of mice, it caused inflammation by recruiting neutrophils. Accordingly, when cells from the peritoneal cavity are incubated with FasL, they produced IL-1β while undergoing apoptosis. These results suggested that the apoptotic cells recruit inflammatory cells to clean up the corps.