Radiation and stress-induced apoptosis: A role for Fas/Fas ligand interactions

The Ipr gene encodes a defective form of Fas, a cell surface protein that mediates apoptosis, This defect blocks apoptotic deletion of autoreactive T and B cells, leading to lymphoproliferation and lupus-like autoantibody production, The effects of the Ipr Fas mutation on other kinds of physiologically relevant apoptosis are largely undocumented, To assess whether some of the apoptosis known to occur after ionizing radiation might be mediated by Fas/Fas ligand (FasL) interactions, we quantitated in vitro apoptosis by flow cytometry measurement of DNA content in splenic T and B cells from irradiated 5- to 8-month-old B6/lpr mice, Total apoptosis of both Ipr and control cells was substantial after treatment; however there was a significant difference between B6 (73%) and Ipr (25%) lymphocyte apoptosis, Thy1, CD4, CD8, and IgM cells from Ipr showed much lower levels of apoptosis than control cells after irradiation, Apoptosis induced by heat shock was also impaired in [pr, The finding that gamma-irradiation increased Fas expression on B6 cells and that irradiation-induced apoptosis could be blocked with a Fas-Fc fusion protein further supported the possible involvement of Fas in this form of apoptosis, Fas/FasL interactions may thus play an important role in identifying and eliminating damaged cells after gamma-irradiation and other forms of injury.