血小板增多症和减少症临床危害严重，有必要对血小板产生调控机制开展研究。最新研究显示肺部存在血小板前体细胞巨核细胞，其生成的血小板数量约占机体的50%。我们前期实验利用活体双光子显微镜观察验证了小鼠肺部巨核细胞产生血小板的过程，并意外发现输注抗糖蛋白GPIb-IX-V亚基GPIbα的抗体可明显促进小鼠肺部巨核细胞生成前血小板；我们利用点突变和免疫沉淀技术发现GPIbα结合Moesin蛋白可能与GPIbα调控血小板产生作用相关。鉴于Moesin在细胞膜延伸突出中的重要作用，我们推断GPIbα可能通过结合Moesin在巨核细胞伸出伪足产生前血小板过程发挥重要作用。在本申请中，我们将利用抗体表位筛选、生化细胞技术，双光子显微镜结合Microfluidic技术从体内和体外对GPIbα亚基通过Moesin调控巨核细胞生成前血小板的作用机制开展研究，为增多症和减少症临床的治疗提供新理论。

The clinical risk of thrombocytosis and thrombocytopenia is serious, and it is necessary to conduct research on the regulation mechanism of platelet production. The latest research has shown that platelet precursor cell megakaryocytes in the lungs. The contribution of the lungs to platelet biogenesis is substantial, accounting for approximately 50% of total platelet production. Our previous experiments demonstrated the process of platelet production in mouse lung megakaryocytes by in vivo two-photon microscopy, and unexpectedly found that infusion of anti-glycoprotein GPIb-IX-V subunit GPIbα antibody can significantly promote megakaryocyte produce more pro/pre-platelets in mouse lung. We used point mutations and immunoprecipitation techniques to find that GPIbα binding to Moesin protein may be associated with GPIbα regulation of platelet production. In view of the important role of Moesin in the elongation of cell membranes, we conclude that GPIbα may play an important role in the pro/pre-platelet process by binding Moesin during the pseudopodium of megakaryocytes process. In this application, we will use antibody epitope screening, biochemical cell technology, two-photon microscopy combined with Microfluidic technology to study the mechanism of GPIbα subunits through Moesin to regulate the megakaryocyte pro/pre-platelet formation in vivo and in vitro, which will provide new concept for the clinical treatment for platelet increased and decreased disease.