Reap E A, Roof K, Maynor K, Borrero M, Booker J, Cohen P L
Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7280, USA.
Proc Natl Acad Sci U S A. 1997 May 27;94(11):5750-5. doi: 10.1073/pnas.94.11.5750.
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.
lpr基因编码一种有缺陷的Fas形式，Fas是一种介导细胞凋亡的细胞表面蛋白。这种缺陷会阻断自身反应性T细胞和B细胞的凋亡性清除，导致淋巴细胞增殖和产生狼疮样自身抗体。lpr Fas突变对其他类型生理相关凋亡的影响在很大程度上尚无文献记载。为了评估已知在电离辐射后发生的某些凋亡是否可能由Fas/Fas配体（FasL）相互作用介导，我们通过流式细胞术测量5至8月龄B6/lpr小鼠脾脏T细胞和B细胞中的DNA含量，对体外凋亡进行了定量。处理后，lpr细胞和对照细胞的总凋亡率都很高；然而，B6（73%）和lpr（25%）淋巴细胞凋亡之间存在显著差异。照射后，lpr的Thy1、CD4、CD8和IgM细胞的凋亡水平远低于对照细胞。热休克诱导的凋亡在lpr中也受损。γ射线照射增加了B6细胞上Fas的表达，并且照射诱导的凋亡可以被Fas-Fc融合蛋白阻断，这一发现进一步支持了Fas可能参与这种凋亡形式。因此，Fas/FasL相互作用可能在识别和清除γ射线照射及其他形式损伤后的受损细胞中发挥重要作用。
