Li Ming O, Sarkisian Matthew R, Mehal Wajahat Z, Rakic Pasko, Flavell Richard A
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Science. 2003 Nov 28;302(5650):1560-3. doi: 10.1126/science.1087621.
Cells undergoing apoptosis during development are removed by phagocytes, but the underlying mechanisms of this process are not fully understood. Phagocytes lacking the phosphatidylserine receptor (PSR) were defective in removing apoptotic cells. Consequently, in PSR-deficient mice, dead cells accumulated in the lung and brain, causing abnormal development and leading to neonatal lethality. A fraction of PSR knockout mice manifested a hyperplasic brain phenotype resembling that of mice deficient in the cell death-associated genes encoding Apaf-1, caspase-3, and caspase-9, which suggests that phagocytes may also be involved in promoting apoptosis. These data demonstrate a critical role for PSR in early stages of mammalian organogenesis and suggest that this receptor may be involved in respiratory distress syndromes and congenital brain malformations.
在发育过程中经历凋亡的细胞会被吞噬细胞清除，但其潜在机制尚未完全明确。缺乏磷脂酰丝氨酸受体（PSR）的吞噬细胞在清除凋亡细胞方面存在缺陷。因此，在PSR基因敲除小鼠中，死亡细胞在肺和脑中积聚，导致发育异常并引起新生小鼠死亡。一部分PSR基因敲除小鼠表现出脑增生表型，类似于缺乏编码凋亡蛋白酶激活因子-1（Apaf-1）、半胱天冬酶-3和半胱天冬酶-9的细胞死亡相关基因的小鼠，这表明吞噬细胞可能也参与促进细胞凋亡。这些数据证明了PSR在哺乳动物器官发生早期阶段的关键作用，并表明该受体可能与呼吸窘迫综合征和先天性脑畸形有关。
