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 t hat mediates apoptosis, This defect blocks apoptotic deletion of autor eactive T and B cells, leading to lymphoproliferation and lupus-like a utoantibody production, The effects of the Ipr Fas mutation on other k inds of physiologically relevant apoptosis are largely undocumented, T o assess whether some of the apoptosis known to occur after ionizing r adiation might be mediated by Fas/Fas ligand (FasL) interactions, we q uantitated in vitro apoptosis by flow cytometry measurement of DNA con tent 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 a fter treatment; however there was a significant difference between B6 (73%) and Ipr (25%) lymphocyte apoptosis, Thy1, CD4, CD8, and IgM cell s from Ipr showed much lower levels of apoptosis than control cells af ter 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 Fa s in this form of apoptosis, Fas/FasL interactions may thus play an im portant role in identifying and eliminating damaged cells after gamma- irradiation and other forms of injury.