Ma Dongchu, Sun Yinghui, Lin Di, Wang Haoyang, Dai Bing, Zhang Xinghai, Ouyang Weiming, Jian Jinlong, Jia Wei, Xu Xiaoguang, Jin Boquan
Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Eur J Haematol. 2005 Mar;74(3):228-40. doi: 10.1111/j.1600-0609.2004.00345.x.
In this study, we examined the expression of CD226 on megakaryocytic, granulocytic and erythroid lineage from hematopoietic stem cells/progenitor cells in adult and fetus and its potential role in megakaryocytic maturation.
CD34(+) cells from adult and fetus were induced to differentiate toward the megakaryocytic lineage by thrombopoietin (TPO) and the granulocytic lineage by granulocyte colony-stimulating factor (G-CSF), respectively. Mononuclear cells from fetal liver and CD34(+) cells from adult were induced to differentiate toward erythroid-lineage by erythropoiesis (EPO). We investigated the expression of CD226 and lymphocyte function associated antigen-1 (LFA-1) (CD11a) during hemopoiesis. We also studied the effect of CD226 monoclonal antibody (MoAb) and LFA-1 MoAb on megakaryocyte with antibody cross-liking technique.
CD34(+) cells from adult and fetus and TPO-induced CD41(+) cells all expressed CD226 molecule. CD226 was not expressed on erythroid progenitor cells and erythroblasts and most cells of granulocytic lineage although G-CSF induced a significant increase of the expression of CD226 on CD34(+) cells in early period of time. CD226 MoAb acts on megakaryocytes by inducing intracellular calcium mobilization. The expression of LFA-1 decreased significantly at late stage of differentiation and maturation of fetal megakaryocytes whereas the expression of LFA-1 on adult megakaryocytes retained at a high level. CD226 MoAb in combination with LFA-1 MoAb shifted the ploidy of generated megakaryocytes from adult-derived CD34(+) cells to higher classes significantly although CD226 and LFA-1 MoAb slightly increased the ploidy of the generated megakaryocytes individually. CD226 MoAb or LFA-1 MoAb or CD226 MoAb plus LFA-1 MoAbs did not increase the ploidy of the generated megakaryocytes from fetus-derived CD34(+) cells.
CD226 molecules play an important role in maturation of the megakaryocytes in combination with LFA-1.
在本研究中,我们检测了成人及胎儿造血干细胞/祖细胞来源的巨核细胞系、粒细胞系和红系细胞中CD226的表达情况及其在巨核细胞成熟过程中的潜在作用。
分别用血小板生成素(TPO)诱导成人及胎儿的CD34(+)细胞向巨核细胞系分化,用粒细胞集落刺激因子(G-CSF)诱导其向粒细胞系分化。用促红细胞生成素(EPO)诱导胎儿肝脏的单个核细胞及成人的CD34(+)细胞向红系分化。我们研究了造血过程中CD226和淋巴细胞功能相关抗原-1(LFA-1,CD11a)的表达情况。我们还通过抗体交联技术研究了CD226单克隆抗体(MoAb)和LFA-1 MoAb对巨核细胞的影响。
成人及胎儿的CD34(+)细胞以及TPO诱导的CD41(+)细胞均表达CD226分子。红系祖细胞、成红细胞以及粒细胞系的大多数细胞均不表达CD226,尽管G-CSF在早期可诱导CD34(+)细胞上CD226的表达显著增加。CD226 MoAb通过诱导细胞内钙动员作用于巨核细胞。胎儿巨核细胞分化成熟后期LFA-1的表达显著降低,而成人巨核细胞上LFA-1的表达维持在较高水平。虽然CD226和LFA-1 MoAb单独作用时可轻微增加所生成巨核细胞的倍性,但CD226 MoAb与LFA-1 MoAb联合使用可使成人来源的CD34(+)细胞所生成巨核细胞的倍性显著向更高类别转变。CD226 MoAb或LFA-1 MoAb或CD226 MoAb加LFA-1 MoAbs均未增加胎儿来源的CD34(+)细胞所生成巨核细胞的倍性。
CD226分子与LFA-1共同在巨核细胞成熟过程中发挥重要作用。