CIRCULATING BFU-E HETEROGENEITY IN SICKLE CELL ANEMIA

镰状细胞性贫血中循环 BFU-E 的异质性

• 批准号: 5213669
• 负责人: HELENA P CROIZAT
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5213669
• 关键词: antibody neutralization test; bioassay; cell cycle; cell growth regulation; colony stimulating factor; cytokine receptors; enzyme linked immunosorbent assay; erythroid stem cell; erythropoiesis; erythropoietin; flow cytometry; growth factor receptors; growth inhibitors; growth media; hematology; hematopoietic growth factor; hemoglobin F; human tissue; interleukin 3; monocyte; radioimmunoassay; sickle cell anemia; tissue /cell culture; transforming growth factors

The present proposal is based on our previous studies which demonstrated that peripheral BFU-E in sickle cell anemia patients varied in their characteristics according to the peripheral percent of HbF. Specifically, low HbF patients (< 9%), have a higher number of BFU-E, with a high proportion of these BFU-E in active cycling and adherent mononuclear cells obtained from these patients constitutively produce BPA. More recent work has demonstrated that GM-CSF is either the sole or most important component of this BPA activity. In addition, preliminary data demonstrates that light density mononuclear cells harvested from peripheral blood of high HbF SS patients (> 9%) produce negative growth factors for BFU-E. Finally, using delayed addition of EpO we have detected heterogeneity in the intrinsic characteristics of BFU-E in SS disease: some BFU-E are sensitive to EpO alone, others to GM-CSF and IL-3 and yet others to IL-3 alone. The heterogeneity also varies with peripheral HbF levels. The SPECIFIC AIMS of this proposal are the following: What are the positive growth factors involved in BPA derived from the adherent cells that affect BFU-E in low HbF SS patients? Besides GM-CSF, is IL-3 involved? What are the negative growth factors involved in the regulation of BFU-E in sickle cell anemia patients with high HbF?; Are GM-CSF, and other growth factors, found in detectable levels in blood of sickle cell anemia patients? Is this related with HB F levels?; Using the strategy of delayed addition of EpO to distinguish populations of BFU-E according to their differential sensitivity to EpO, GM-CSF and IL-3, ask: Do patients with sickle cell anemia have populations of BFU-E with diverse sensitivities to growth factors? If so, how is the distribution of growth factor sensitivities correlated with HbF and other hematological parameters of SS disease?

目前的建议是基于我们之前的研究，该研究表明 镰状细胞性贫血患者的外周血 BFU-E 存在差异 根据 HbF 外周百分比的特征。 具体来说，低 HbF 患者 (< 9%) 的 BFU-E 数量较高， 这些 BFU-E 在主动循环和粘附中的比例很高 从这些患者获得的单核细胞组成型产生 双酚 A。 最近的研究表明，GM-CSF 是唯一的 或该 BPA 活动的最重要组成部分。 此外， 初步数据表明，光密度单核细胞 从高 HbF SS 患者 (> 9%) 的外周血中采集产生 BFU-E 的负生长因子。 最后，使用延迟添加 我们发现 EpO 的内在特征存在异质性 SS 疾病中的 BFU-E：一些 BFU-E 仅对 EpO 敏感，另一些对 EpO 敏感 GM-CSF 和 IL-3 以及其他单独的 IL-3。 异质性也 随外周 HbF 水平变化。 本提案的具体目标 以下是： BPA 涉及哪些积极的增长因素 来自影响低 HbF SS 患者 BFU-E 的贴壁细胞？ 除了GM-CSF之外，还有IL-3吗？ 负增长因素有哪些 参与镰状细胞性贫血患者 BFU-E 的调节 高 HbF？； GM-CSF 和其他生长因子是否可检测到？ 镰状细胞性贫血患者血液中的水平？ 这和HB有关系吗 F级？；采用延迟添加EpO的策略来区分 BFU-E 群体根据其对 EpO 的不同敏感性， GM-CSF和IL-3，请问：镰状细胞性贫血患者有吗？ 对生长因子具有不同敏感性的 BFU-E 群体？ 如果 那么，生长因子敏感性的分布是如何相关的 与 SS 疾病的 HbF 和其他血液学参数有关吗？