Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor
Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor
复制标题
DOI：
10.1182/blood-2003-09-3245
复制
发表时间：
2004-05-01
期刊：
影响因子：
20.3
通讯作者：
Fukui, Y
中科院分区：
文献类型：
--
作者：
Kunisaki, Y;Masuko, S;Fukui, Y
巨噬细胞清除凋亡细胞被认为是预防导致组织损伤的炎症反应的重要因素。磷脂酰丝氨酸受体(PSR)与暴露在凋亡细胞表面的磷脂酰丝氨酸(PS)特异性结合，在体外介导对凋亡细胞的摄取，但PSR的生理相关性尚不清楚。这个问题通过产生PSR缺陷(PSR-/-)小鼠来解决。PSR-/-小鼠表现出严重的贫血，并在围产期死亡。在PSR-/-胎肝中，红系分化在早期红系细胞阶段被阻止。此外，PSR-/-胚胎由于T淋巴样细胞的发育缺陷而表现出胸腺萎缩。在PSR-/-胚胎的肝脏和胸腺中，巨噬细胞对凋亡细胞的清除均受到损害。然而，这并没有诱导炎性细胞因子的上调。这些结果表明，在胚胎发育过程中，PSR介导的凋亡细胞摄取对于确定的红细胞生成和T淋巴细胞生成是必需的，而不是预防炎症反应。(C)2004年，由美国血液病学会提供。
Clearance of apoptotic cells by macrophages is considered important for prevention of inflammatory responses leading to tissue damage. The phosphatidylserine receptor (PSR), which specifically binds to phosphatidylserine (PS) exposed on the surface of apoptotic cells, mediates uptake of apoptotic cells in vitro, yet the physiologic relevance of PSR remains unknown. This issue was addressed by generating PSR- deficient (PSR-/-) mice. PSR-/- mice exhibited severe anemia and died during the perinatal period. In the PSR-/- fetal livers, erythroid differentiation was blocked at an early erythroblast stage. In addition, PSR-/- embryos exhibited thymus atrophy owing to a developmental defect of T-lymphoid cells. Clearance of apoptotic cells by macrophages was impaired in both liver and thymus of PSR-/- embryos. However, this did not induce up-regulation of inflammatory cytokines. These results indicate that during embryonic development, PSR-mediated apoptotic cell uptake is required for definitive erythropoiesis and T lymphopoiesis, independently of the prevention of inflammatory responses. (C) 2004 by The American Society of Hematology.