Radiation and stress-induced apoptosis: a role for Fas/Fas ligand interactions.
Published
Journal Article
The lpr 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 lpr 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 lpr and control cells was substantial after treatment; however there was a significant difference between B6 (73%) and lpr (25%) lymphocyte apoptosis. Thy1, CD4, CD8, and IgM cells from lpr showed much lower levels of apoptosis than control cells after irradiation. Apoptosis induced by heat shock was also impaired in lpr. 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.
Full Text
Cited Authors
- Reap, EA; Roof, K; Maynor, K; Borrero, M; Booker, J; Cohen, PL
Published Date
- May 27, 1997
Published In
Volume / Issue
- 94 / 11
Start / End Page
- 5750 - 5755
PubMed ID
- 9159145
Pubmed Central ID
- 9159145
International Standard Serial Number (ISSN)
- 0027-8424
Digital Object Identifier (DOI)
- 10.1073/pnas.94.11.5750
Language
- eng
Conference Location
- United States