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

被引:158
作者
Reap, EA
Roof, K
Maynor, K
Borrero, M
Booker, J
Cohen, PL
机构
[1] UNIV N CAROLINA,DEPT MED,DIV RHEUMATOL,CHAPEL HILL,NC 27599
[2] UNIV N CAROLINA,DEPT IMMUNOL MICROBIOL,CHAPEL HILL,NC 27599
关键词
D O I
10.1073/pnas.94.11.5750
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:5750 / 5755
页数:6
相关论文
共 24 条
  • [1] BOSSU P, 1993, J IMMUNOL, V151, P7233
  • [2] APOPTOTIC SIGNALING THROUGH CD95 (FAS/APO-1) ACTIVATES AN ACIDIC SPHINGOMYELINASE
    CIFONE, MG
    DEMARIA, R
    RONCAIOLI, P
    RIPPO, MR
    AZUMA, M
    LANIER, LL
    SANTONI, A
    TESTI, R
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (04) : 1547 - 1552
  • [3] Cohen Philip L., 1995, P169
  • [4] LPR AND GLD - SINGLE GENE MODELS OF SYSTEMIC AUTOIMMUNITY AND LYMPHOPROLIFERATIVE DISEASE
    COHEN, PL
    EISENBERG, RA
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1991, 9 : 243 - 269
  • [5] FEATURES OF APOPTOTIC CELLS MEASURED BY FLOW-CYTOMETRY
    DARZYNKIEWICZ, Z
    BRUNO, S
    DELBINO, G
    GORCZYCA, W
    HOTZ, MA
    LASSOTA, P
    TRAGANOS, F
    [J]. CYTOMETRY, 1992, 13 (08): : 795 - 808
  • [6] THE FAS PROTEIN IS EXPRESSED AT HIGH-LEVELS ON CD4+CD8+ THYMOCYTES AND ACTIVATED MATURE LYMPHOCYTES IN NORMAL MICE BUT NOT IN THE LUPUS-PRONE STRAIN, MRL LPR/LPR
    DRAPPA, J
    BROT, N
    ELKON, KB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) : 10340 - 10344
  • [7] FAS LIGATION INDUCES APOPTOSIS OF CD40-ACTIVATED HUMAN B-LYMPHOCYTES
    GARRONE, P
    NEIDHARDT, EM
    GARCIA, E
    GALIBERT, L
    VANKOOTEN, C
    BANCHEREAU, J
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (05) : 1265 - 1273
  • [8] FAS-INDUCED APOPTOSIS IS MEDIATED VIA A CERAMIDE-INITIATED RAS SIGNALING PATHWAY
    GULBINS, E
    BISSONNETTE, R
    MAHBOUBI, A
    MARTIN, S
    NISHIOKA, W
    BRUNNER, T
    BAIER, G
    BAIERBITTERLICH, G
    BYRD, C
    LANG, F
    KOLESNICK, R
    ALTMAN, A
    GREEN, D
    [J]. IMMUNITY, 1995, 2 (04) : 341 - 351
  • [9] IONIZING-RADIATION ACTS ON CELLULAR MEMBRANES TO GENERATE CERAMIDE AND INITIATE APOPTOSIS
    HAIMOVITZFRIEDMAN, A
    KAN, CC
    EHLEITER, D
    PERSAUD, RS
    MCLOUGHLIN, M
    FUKS, Z
    KOLESNICK, RN
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (02) : 525 - 535
  • [10] ILLERA VA, 1993, J IMMUNOL, V151, P2965