CHARACTERIZATION OF HUMAN MEGAKARYOCYTE CELL LINES

具有巨核细胞特性的细胞系已经从 正常供体和骨髓增生性疾病患者的血液。 我们要求提供资金，以充分说明这些路线的特点。 而且 培养的巨核细胞对病毒感染的易感性 将全面调查病毒进入、复制和 在血小板前体细胞中产生。 细胞系将用于 制备针对所选巨核细胞的单克隆抗体和/或 血小板抗原 这些试剂将用于（1）鉴定 存在于正常血液中的巨核细胞的循环前体; (2)识别白血病细胞制备物中的巨核母细胞和（3） 研究这些细胞系和短期培养细胞的分化， 完全成熟的巨核细胞。 细胞系将提供 首次研究血小板合成的机会 糖蛋白IIb/IIIa和纤维蛋白原在细胞中的密切相关 与巨核细胞相同。 这些研究的结果将深刻影响我们对 巨核细胞和血小板分化，就像T细胞的培养一样 主要研究者所做的。 该提案将产生细胞 科学界普遍感兴趣的路线。 这项建议会 也产生重要的单克隆抗体，用于鉴定 异源细胞群中的巨核细胞前体细胞。 最后， 这项提议将产生重要的信息， 巨核细胞生成和人类先天性 血小板缺陷

Cells lines with properties of megakaryocytes have been established from the blood of normal donors and patients with myeloproliferative disorders. We request funds to fully characterize these lines. Furthermore, the susceptibility of the cultured megakaryocytes to infection with viruses will be fully investigated as to the mode of virus entry, replication and production in platelet precursor cells. The cell lines will be used to prepare monoclonal antibodies against selected megakaryocyte and/or platelet antigens. These reagents will be used (1) to identify the circulating precursor to megakaryocytes which is present in normal blood; (2) to recognize the megakaryoblast in leukemia cell preparations and (3) to study differentiation of these cell lines and short-term cultured cells towards fully mature megakaryocytes. The cell lines will offer the opportunity to study for the first time the synthesis of platelet glycoprotein IIb/IIIa and of fibrinogen in cells which are closely related to or are the same as megakaryocytes. The results of these studies will profoundly influence our understanding of megakaryocyte and platelet differentiation, just as the culture of T cells by the Principal Investigator has done. The proposal will generate cell lines of general interest to the scientific community. This proposal will also yield important monoclonal antibodies for the identification of megakaryocyte precursors among heterogeneous cell populations. Finally, the proposal will yield significant information into the physiology of megakaryocytopoiesis and into the pathophysiology of human congenital platelet defects.