CHARACTERIZATION OF HUMAN MEGAKARYOCYTE CELL LINES

已建立具有巨核细胞特性的细胞系 正常献血者和骨髓增生性疾病患者的血液。 我们需要资金来充分描述这些线路的特征。此外， 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、复制和传播的方式 在血小板前体细胞中产生。这些细胞系将被用于 制备抗选定巨核细胞和/或 血小板抗原。这些试剂将用于(1)鉴定 巨核细胞的循环前体，存在于正常血液中； (2)白血病细胞制剂中巨核细胞的识别和(3) 研究这些细胞系与短期培养细胞的分化 走向完全成熟的巨核细胞。这些细胞系将提供 首次研究血小板合成的机会 糖蛋白IIb/IIIa与细胞内纤维蛋白原密切相关 属于或等于巨核细胞。 这些研究的结果将深刻地影响我们对 巨核细胞和血小板分化，就像T细胞的培养一样 由首席调查员所做的。该提案将生成单元格 科学界普遍感兴趣的领域。这项提议将 也产生了重要的单抗，用于鉴定 异质细胞群体中的巨核细胞前体。最后， 这项提议将为人类的生理学提供重要的信息 巨核细胞生成及其在人类先天性疾病中的作用 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.