Tissue uptake of circulating thrombopoietin is increased in immune-mediated compared with irradiated thrombocytopenic mice.

摘要: We have previously demonstrated a significant inverse correlation between circulating thrombopoietin (TPO) levels and peripheral platelet (PLT) counts in patients with thrombocytopenia secondary to megakaryocytic hypoplasia but not immune thrombocytopenic purpura (ITP; Chang et al, Blood 88:3354, 1996). To test the hypothesis that differences TPO these two types of are caused by total capacity Mpl receptor-mediated clearance, was induced female CD-1 mice either sublethal irradiation (irradiated) or rabbit antimouse PLT serum (RAMPS) for 1 day (1 d RAMPS) 5 days (5 RAMPS). A well-characterized murine model autoimmune purpura, male (NZW × BXSB) F1 (W/B F1), also included this study. All their controls received trace amounts 125I-recombinant (125I-rmTPO) intravenously were killed 3 hours postinjection. cell-associated radioactivity significantly decreased all 4 groups mice. Significantly increased plasma whole spleen-associated observed irradiated group compared ( P < .05). While lesser still increase decrease RAMPS .05), there no nor W/B controls, although higher F1male. F1male r = −.91, n 6, There bone (femur)/blood-associated .01). Furthermore, 125I-rmTPO uptake within spleen marrow appeared be associated mass when tissue samples examined light microscopy. Internalization megakaryocytes PLTs spleens marrows ITP directly using electron microscopic autoradiography. Labeled found splenic macrophages. Additionally, mean volumes than those control as bound (cpm) per million Finally, degradation products only animals These data suggest lack Mpl+ cells results levels. that, after brief surge response RAMPS), an during steady-state + male) is due, at least part, its high turnover megakaryocytes.