Transendothelial migration of megakaryocytes in response to stromal cell-derived factor 1 (SDF-1) enhances platelet formation.
Transendothelial migration of megakaryocytes in response to stromal cell-derived factor 1 (SDF-1) enhances platelet formation.
复制标题
巨核细胞对基质细胞衍生因子1（SDF-1）的跨内皮迁移增强了血小板的形成。
DOI：
10.1084/jem.188.3.539
复制
发表时间：
1998-08-03
影响因子：
15.3
通讯作者：
Rafii, S
中科院分区：
文献类型：
--
作者：
Hamada, T;Mohle, R;Hesselgesser, J;Hoxie, J;Nachman, R L;Moore, M A;Rafii, S
尽管血小板生成素已被证明可以促进巨核细胞（MK）的增殖和成熟，但血小板形成的确切机制和部位尚未明确。研究表明，MK可通过骨髓内皮细胞（BMEC）迁移，并在窦隙或肺毛细血管内释放血小板。在寻找可能介导MK迁移的趋化因子时，我们发现成熟的多倍体MK表达G蛋白偶联趋化因子受体CXCR 4（Fusin，LESTR）。因此，我们探讨了基质细胞衍生因子1（SDF-1），CXCR 4的配体，也可能诱导成熟MK的跨内皮迁移。SDF-1，而不是其他CXC或CC趋化因子，能够介导MK迁移（ED 50 = 125 pmol/L）。SDF-1诱导的MK趋化性被CXCR 4特异性mAb（12 G5）和百日咳毒素抑制，表明通过G蛋白偶联受体CXCR 4的信号传导是迁移所必需的。SDF-1还通过增加MK对BMEC的亲和力诱导MK迁移通过BMEC的汇合单层。用白细胞介素1β激活BMEC导致响应SDF-1的MK迁移增加3倍。中和内皮特异性粘附分子E-选择素的mAb阻断了50%的MK迁移，表明MK与BMEC的细胞相互作用对MK的迁移至关重要。光学显微镜和倍性测定证明易位的MK以多倍体MK为主。几乎所有在下腔室中产生的血小板也表达CXCR 4。在下室形成的血小板是功能性的，并表达P-选择素（CD 62 P）响应凝血酶刺激。电子显微镜下的细胞迁移通过BMEC单层的SDF-1的反应证明了完整的多倍体MK以及血小板形成过程中的MK的存在。这些结果表明，SDF-1是一个强大的趋化因子成熟的MK。CXCR 4的表达可能是MKs迁移和血小板形成的关键细胞信号。
Although thrombopoietin has been shown to promote megakaryocyte (MK) proliferation and maturation, the exact mechanism and site of platelet formation are not well defined. Studies have shown that MKs may transmigrate through bone marrow endothelial cells (BMEC), and release platelets within the sinusoidal space or lung capillaries. In search for chemotactic factor(s) that may mediate transmigration of MKs, we have discovered that mature polyploid MKs express the G protein–coupled chemokine receptor CXCR4 (Fusin, LESTR). Therefore, we explored the possibility that stromal cell–derived factor 1 (SDF-1), the ligand for CXCR4, may also induce transendothelial migration of mature MKs. SDF-1, but not other CXC or CC chemokines, was able to mediate MK migration (ED50 = 125 pmol/liter). The MK chemotaxis induced by SDF-1 was inhibited by the CXCR4-specific mAb (12G5) and by pertussis toxin, demonstrating that signaling via the G protein–coupled receptor CXCR4 was necessary for migration. SDF-1 also induced MKs to migrate through confluent monolayers of BMEC by increasing the affinity of MKs for BMEC. Activation of BMEC with interleukin 1β resulted in a threefold increase in the migration of MKs in response to SDF-1. Neutralizing mAb to the endothelial-specific adhesion molecule E-selectin blocked the migration of MKs by 50%, suggesting that cellular interaction of MKs with BMEC is critical for the migration of MKs. Light microscopy and ploidy determination of transmigrated MKs demonstrated predominance of polyploid MKs. Virtually all platelets generated in the lower chamber also expressed CXCR4. Platelets formed in the lower chamber were functional and expressed P-selectin (CD62P) in response to thrombin stimulation. Electron microscopy of the cells that transmigrated through the BMEC monolayers in response to SDF-1 demonstrated the presence of intact polyploid MKs as well as MKs in the process of platelet formation. These results suggest that SDF-1 is a potent chemotactic factor for mature MKs. Expression of CXCR4 may be the critical cellular signal for transmigration of MKs and platelet formation.