Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Blood. 2010 Sep 9;116(10):1776-8. doi: 10.1182/blood-2009-12-259663. Epub 2010 Jun 7.
The mechanisms responsible for the brief life span of blood platelets have been a subject of speculation since the 1950s. The most popular hypothesis to date has been the "multiple-hit" model, whereby damage inflicted by external "hits" triggers recognition and clearance by the reticuloendothelial system. Recently, it was demonstrated that platelets contain an apoptotic pathway that mediates their survival in vivo. Using a novel labeling technique to measure population and cohort survival in mice carrying mutations in this pathway, combined with mathematical modeling, we have studied the internal and external control of platelet fate. Our results cast doubt on the veracity of the multiple-hit model. An alternative model, under which platelets are born with an internal "timer," provides a more parsimonious interpretation of the data. Thus, at steady state, platelet senescence is probably the product of internal processes rather than external hits.
自 20 世纪 50 年代以来，血小板寿命短暂的机制一直是推测的主题。迄今为止，最流行的假说一直是“多次打击”模型，即外部“打击”造成的损伤触发网状内皮系统的识别和清除。最近，有人证明血小板含有凋亡途径，介导其在体内的存活。我们使用一种新的标记技术来测量携带该途径突变的小鼠中的群体和队列存活，结合数学建模，我们研究了血小板命运的内部和外部控制。我们的结果对多次打击模型的准确性提出了质疑。在另一种模型中，血小板带有内部“定时器”，这种模型更简洁地解释了数据。因此，在稳定状态下，血小板衰老可能是内部过程而不是外部打击的产物。
