Abrams Kraig, Yunusov Murad Y, Slichter Sherrill, Moore Peter, Nelp Wil B, Burstein Samuel A, McDonough Sean, Durack Lawrence, Storer Barry, Storb Rainer, Gass M John, Georges George, Nash Richard A
Puget Sound Blood Center, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109-1024, USA.
Br J Haematol. 2003 May;121(4):614-22. doi: 10.1046/j.1365-2141.2003.04313.x.
To characterize recombinant human macrophage-colony stimulating factor (rhM-CSF)-associated thrombocytopenia (TCP), in vivo studies were performed in dogs, including the biodistributions and recoveries of radiolabelled autologous and allogeneic platelets. rhM-CSF induced a reversible, dose-dependent decrease in platelet counts. The number of megakaryocytes in spleen and marrow of rhM-CSF-treated dogs was increased two to threefold. Recoveries of allogeneic platelets transfused from rhM-CSF-treated donors into tolerized recipients (n = 3) were not significantly different from allogeneic baseline studies (93 +/- 10% of baseline values at 24 h and 90 +/- 1% at 40 h), whereas autologous platelets infused back into rhM-CSF-treated donors had decreased recoveries (45 +/- 2% of baseline values at 24 h, P = 0.03 and 20 +/- 4% at 40 h, P = 0.001). Platelet biodistribution studies showed increased accumulation of radiolabelled platelets over the spleens and livers of rhM-CSF-treated dogs. Histochemistry showed increased levels of platelet-specific antigen (CD41; glycoprotein IIb) associated with Kupffer cells. The sensitivity of platelets from rhM-CSF-treated dogs to activation from thrombin, as measured by expression of P-selectin (CD62P), was not significantly different when compared with baseline studies (P = 0.18; n = 4). These results support the concept that rhM-CSF induces an activation of the monocyte-macrophage system (MMS), which causes a reversible TCP in a dog model.
为了描述重组人巨噬细胞集落刺激因子（rhM-CSF）相关的血小板减少症（TCP），在犬类中进行了体内研究，包括放射性标记的自体和异体血小板的生物分布及回收率。rhM-CSF诱导血小板计数出现可逆的、剂量依赖性下降。接受rhM-CSF治疗的犬类脾脏和骨髓中的巨核细胞数量增加了两到三倍。从接受rhM-CSF治疗的供体输注到耐受受体（n = 3）体内的异体血小板回收率与异体基线研究相比无显著差异（24小时时为基线值的93±10%，40小时时为90±1%），而回输到接受rhM-CSF治疗的供体体内的自体血小板回收率下降（24小时时为基线值的45±2%，P = 0.03；40小时时为20±4%，P = 0.001）。血小板生物分布研究显示，接受rhM-CSF治疗的犬类脾脏和肝脏中放射性标记血小板的蓄积增加。组织化学显示与库普弗细胞相关的血小板特异性抗原（CD41；糖蛋白IIb）水平升高。通过P-选择素（CD62P）表达测量，接受rhM-CSF治疗的犬类血小板对凝血酶激活的敏感性与基线研究相比无显著差异（P = 0.18；n = 4）。这些结果支持了rhM-CSF诱导单核细胞-巨噬细胞系统（MMS）激活的概念，这在犬类模型中导致了可逆的TCP。
