Miura M, Jackson C W, Lyles S A
Blood. 1984 May;63(5):1060-6.
To gain insight into the regulation of megakaryocyte precursors in vivo, we assayed (in vitro) megakaryocyte growth-promoting activity (Meg-GPA) in plasma of rats in which both marrow hypoplasia and thrombocytopenia had been induced by irradiation. Rats received whole body irradiation of 834 rad from a 137Cs source. Plasma was collected at intervals of hours to days, up through day 21 postirradiation, and was tested, at a concentration of 30%, for Meg-GPA on bone marrow cells cultured in 1.1% methylcellulose with 5 X 10(-5) M 2-mercaptoethanol. With normal rat plasma, no megakaryocyte colonies (defined as greater than or equal to 4 megakaryocytes) were seen and only a few single megakaryocytes and clusters (defined as 2 or 3 megakaryocytes) were formed. Two peaks of plasma Meg-GPA were observed after irradiation. The first appeared at 12 hr, before any decrease in marrow megakaryocyte concentration or platelet count. The second occurred on days 10-14 after irradiation, after the nadir in megakaryocyte concentration and while platelet counts were at their lowest levels. A dose-response study of plasma concentration and megakaryocyte growth, using plasma collected 11 days postirradiation, demonstrated that patterns of megakaryocyte growth were related to plasma concentration; formation of single megakaryocytes was optimal over a range of 20%-30% plasma concentration, while cluster and colony formation were optimal at a plasma concentration of 30%. All forms of megakaryocyte growth were decreased with 40% plasma. There was a linear relationship between the number of bone marrow cells plated and growth of single cells, clusters, and colonies using a concentration of 30% plasma collected 11 days after irradiation. We conclude that irradiation causes time-related increases in circulating megakaryocyte growth-promoting activity. We suggest that the irradiated rat is a good model for studying the relationships between Meg-GPA and megakaryocyte and platelet concentration in vivo.
为深入了解体内巨核细胞前体的调节机制，我们检测了经照射诱导骨髓发育不全和血小板减少的大鼠血浆中的巨核细胞生长促进活性（Meg - GPA）（体外检测）。大鼠接受来自137Cs源的834拉德全身照射。在照射后直至第21天期间，每隔数小时至数天采集一次血浆，并以30%的浓度检测其对在含5×10(-5) M 2 - 巯基乙醇的1.1%甲基纤维素中培养的骨髓细胞的Meg - GPA。使用正常大鼠血浆时，未观察到巨核细胞集落（定义为大于或等于4个巨核细胞），仅形成了少数单个巨核细胞和细胞簇（定义为2或3个巨核细胞）。照射后观察到血浆Meg - GPA出现两个峰值。第一个峰值出现在12小时，此时骨髓巨核细胞浓度或血小板计数尚未降低。第二个峰值出现在照射后第10 - 14天，此时巨核细胞浓度处于最低点，而血小板计数处于最低水平。使用照射后11天采集的血浆进行血浆浓度与巨核细胞生长的剂量反应研究表明，巨核细胞生长模式与血浆浓度相关；在20% - 30%的血浆浓度范围内，单个巨核细胞的形成最为理想，而细胞簇和集落形成在30%的血浆浓度时最为理想。当血浆浓度为40%时，所有形式的巨核细胞生长均减少。使用照射后11天采集的30%浓度血浆时，接种的骨髓细胞数量与单个细胞、细胞簇和集落的生长之间存在线性关系。我们得出结论，照射导致循环中的巨核细胞生长促进活性随时间增加。我们认为，受照射的大鼠是研究体内Meg - GPA与巨核细胞及血小板浓度之间关系的良好模型。
