CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development
CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development
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DOI：
10.1182/blood-2011-09-380709
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发表时间：
2012-02-16
期刊：
影响因子：
20.3
通讯作者：
Watson, Steve P.
中科院分区：
文献类型：
--
作者：
Finney, Brenda A.;Schweighoffer, Edina;Watson, Steve P.
C型凝集素受体CLEC-2通过一条关键依赖于酪氨酸激酶Syk的途径发出信号。我们发现，任何一种蛋白质的纯合缺失都会导致脑血管和淋巴发育缺陷、肺膨胀和围产期死亡。此外，我们发现造血谱系中Syk的条件性缺失，或巨核细胞/血小板谱系中CLEC-2或Syk的条件性缺失，也会导致脑血管和淋巴发育的缺陷，尽管小鼠是存活的。相比之下，在其他造血谱系中Syk的条件性缺失对生存力或脑血管和淋巴发育没有影响。我们发现，血小板，但不是血小板释放，调节淋巴管内皮细胞的迁移和细胞间粘附通过依赖于CLEC-2和Syk的途径。这些研究发现，巨核细胞/血小板表达CLEC-2和Syk是正常脑血管和淋巴发育所需的，并且血小板CLEC-2和Syk直接调节体外淋巴内皮细胞行为。（Blood.2012;119（7）：1747-1756）
The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation, and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the hematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other hematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that depends on CLEC-2 and Syk. These studies found that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behavior in vitro. (Blood.2012;119(7):1747-1756)