Hunt P, Hokom M M, Hornkohl A, Wiemann B, Rohde M F, Arakawa T
Laboratory of Stem Cell Biology, Amgen Corporation, Amgen Center, Thousand Oaks, CA 91320.
Exp Hematol. 1993 Aug;21(9):1295-304.
The formation of proplatelet-like processes on megakaryocytes cultured in vitro has been shown to be inhibited by prothrombin, found residually in human serum, which is converted in culture to thrombin. This study reports that another factor found in human serum will counter this inhibition and permit proplatelet-like process formation to occur in vitro even in the presence of inhibitory concentrations of thrombin. The factor was purified from human platelet lysates and identified by amino acid sequence analysis as the proteoglycan serglycin. A similar, if not identical, factor was found at elevated levels in the plasma of thrombocytopenic rabbits. Serglycin probably functions as a proplatelet potentiator by virtue of a tendency to complex with thrombin. Thrombin in complex with serglycin retains its enzymatic properties, but is apparently sterically hindered from interacting with the megakaryocyte cell surface. In preliminary studies, the in vivo administration of serglycin in mice resulted in an increased number of circulating platelets when given in combination with interleukin-6 (IL-6).
体外培养的巨核细胞上血小板样突起的形成已被证明会受到人血清中残留的凝血酶原的抑制，凝血酶原在培养过程中会转化为凝血酶。本研究报告称，人血清中发现的另一种因子可对抗这种抑制作用，即使在存在抑制浓度凝血酶的情况下，也能使体外血小板样突起的形成得以发生。该因子从人血小板裂解物中纯化出来，并通过氨基酸序列分析鉴定为蛋白聚糖丝甘蛋白聚糖。在血小板减少的兔子血浆中发现了一种类似（如果不是完全相同）的因子，其水平升高。丝甘蛋白聚糖可能通过与凝血酶形成复合物的倾向而发挥血小板生成增强剂的作用。与丝甘蛋白聚糖结合的凝血酶保留其酶活性，但显然在空间上受阻而无法与巨核细胞表面相互作用。在初步研究中，给小鼠体内注射丝甘蛋白聚糖并联合白细胞介素 -6（IL -6）时，循环血小板数量增加。
