Giebel Bernd, Corbeil Denis, Beckmann Julia, Höhn Johannes, Freund Daniel, Giesen Kay, Fischer Johannes, Kögler Gesine, Wernet Peter
Institut für Transplantationsdiagnostik and Zelltherapeutika, Heinrich Heine Universität Düsseldorf, Moorenstr 5, Geb 14.80, D-40225 Düsseldorf, Germany.
Blood. 2004 Oct 15;104(8):2332-8. doi: 10.1182/blood-2004-02-0511. Epub 2004 Jul 1.
During ontogenesis and the entire adult life hematopoietic stem and progenitor cells have the capability to migrate. In comparison to the process of peripheral leukocyte migration in inflammatory responses, the molecular and cellular mechanisms governing the migration of these cells remain poorly understood. A common feature of migrating cells is that they need to become polarized before they migrate. Here we have investigated the issue of cell polarity of hematopoietic stem/progenitor cells in detail. We found that human CD34(+) hematopoietic cells (1) acquire a polarized cell shape upon cultivation, with the formation of a leading edge at the front pole and a uropod at the rear pole; (2) exhibit an amoeboid movement, which is similar to the one described for migrating peripheral leukocytes; and (3) redistribute several lipid raft markers including cholesterol-binding protein prominin-1 (CD133) in specialized plasma membrane domains. Furthermore, polarization of CD34(+) cells is stimulated by early acting cytokines and requires the activity of phosphoinositol-3-kinase as previously reported for peripheral leukocyte polarization. Together, our data reveal a strong correlation between polarization and migration of peripheral leukocytes and hematopoietic stem/progenitor cells and suggest that they are governed by similar mechanisms.
在个体发育过程以及整个成年期,造血干细胞和祖细胞都具有迁移能力。与炎症反应中外周白细胞迁移过程相比,调控这些细胞迁移的分子和细胞机制仍知之甚少。迁移细胞的一个共同特征是,它们在迁移前需要极化。在此,我们详细研究了造血干/祖细胞的细胞极性问题。我们发现,人类CD34(+)造血细胞:(1) 在培养时获得极化的细胞形态,在前极形成前缘,在后极形成尾足;(2) 表现出阿米巴样运动,这与描述的迁移外周白细胞的运动相似;(3) 在特殊的质膜结构域中重新分布几种脂筏标记物,包括胆固醇结合蛋白prominin-1(CD133)。此外,如先前报道的外周白细胞极化一样,早期作用的细胞因子可刺激CD34(+)细胞的极化,且这需要磷酸肌醇-3-激酶的活性。总之,我们的数据揭示了外周白细胞与造血干/祖细胞的极化和迁移之间存在很强的相关性,并表明它们受相似机制的调控。