Fielder P J, Gurney A L, Stefanich E, Marian M, Moore M W, Carver-Moore K, de Sauvage F J
Departments of Molecular Oncology, Genentech Inc, South San Francisco, CA USA.
Blood. 1996 Mar 15;87(6):2154-61.
The involvement of platelets and the c-mpl receptor in the regulation of thrombopoietin (TPO) plasma concentrations and tissue mRNA levels was investigated in both normal mice and mice defective in c-mpl (c-mpl-/-). Although c-mpl-/- mice have fewer platelets and higher plasma TPO activity than normal mice, there was no increase in TPO mRNA levels as measured by an S1 nuclease protection assay. After the intravenous injection of 125I-TPO, specific uptake of radioactivity by the spleen and blood cells was present in the normal mice, but absent in the c-mpl-/- mice. Platelet-rich plasma (PRP) from normal mice was able to bind and internalize 125I-TPO, whereas PRP from c-mpl-/- mice lacked this ability. Analysis of 125I-TPO binding to normal PRP indicated that binding was specific and saturable, with an approximate affinity of 560 pmol/L and 220 receptors per platelet. PRP from normal mice was also able to degrade 125I-TPO into lower molecular weight fragments. After the intravenous injections, c-mpl-/- mice cleared a dose of 125I-TPO at a much slower rate than did normal mice. Injection of washed platelets from normal mice into c-mpl-/- mice resulted in a dramatic, but transient, decrease in plasma TPO levels. These data provide evidence that platelets regulate plasma TPO levels via binding to the c-mpl receptor on circulating platelets.
在正常小鼠和c-mpl基因缺陷小鼠（c-mpl-/-）中，研究了血小板和c-mpl受体在血小板生成素（TPO）血浆浓度调节及组织mRNA水平调节中的作用。尽管c-mpl-/-小鼠的血小板数量比正常小鼠少，血浆TPO活性比正常小鼠高，但通过S1核酸酶保护试验检测，TPO mRNA水平并未升高。静脉注射125I-TPO后，正常小鼠的脾脏和血细胞出现放射性的特异性摄取，而c-mpl-/-小鼠则没有。正常小鼠的富血小板血浆（PRP）能够结合并内化125I-TPO，而c-mpl-/-小鼠的PRP缺乏这种能力。对125I-TPO与正常PRP结合的分析表明，这种结合具有特异性和饱和性，亲和力约为560 pmol/L，每个血小板有220个受体。正常小鼠的PRP还能够将125I-TPO降解为分子量更低的片段。静脉注射后，c-mpl-/-小鼠清除一定剂量125I-TPO的速度比正常小鼠慢得多。将正常小鼠的洗涤血小板注射到c-mpl-/-小鼠体内，导致血浆TPO水平急剧但短暂下降。这些数据证明血小板通过与循环血小板上的c-mpl受体结合来调节血浆TPO水平。
