CD47-SIRPα在人类红细胞老化与吞噬过程中的作用  

Role of CD47-SIRPα signaling in the senescence and clearance of human red blood cells

作　　者：周洁[1,2] 李勤[1] 朱自严[1] 

机构地区：[1]上海市血液中心,上海200051 [2]华东师范大学生命科学学院,上海200062

出　　处：《现代免疫学》2011年第5期409-414,共6页Current Immunology

基　　金：上海市自然科学基金项目(07ZR14098;09ZR1429300)

摘　　要：探讨CD47-SIRPα在人类红细胞衰老与吞噬过程中的作用。采用Western blot检测体外4℃和37℃保存红细胞(RBC)及老化过程中红细胞膜上CD47的表达量;用单核细胞单层分析试验(monocyte monolayer assay,MMA)观察人THP-1单核细胞系对不同年龄段红细胞和CD47抗体F(ab’)2端封闭红细胞的吞噬情况及Western blot检测THP-1细胞上SIRPα磷酸化情况。结果发现,无论是在体内老化还是体外老化过程中,红细胞膜上CD47的表达量均出现显著下降趋势,随着保存时间的延长,CD47的表达量最大可下降82.64%(4℃保存情况下);THP-1细胞对不同年龄段红细胞的吞噬情况存在差异性,更易吞噬年老红细胞,吞噬率为35.32%,对年轻红细胞的吞噬率为13.72%(n=7,P<0.02);对新鲜红细胞的吞噬率为2.22%,对CD47抗体F(ab’)2端封闭红细胞的吞噬率为31.51%(n=7,P<0.02);吞噬不同年龄段红细胞后,THP-1细胞上磷酸化SIRPα量不同,与吞噬年轻红细胞相比,吞噬年老红细胞后,磷酸化SIRPα的量下降了57.12%。表明人类红细胞的老化与吞噬过程和CD47-SIRPα相互作用存在密切关系。To investigate the role of CD47-SIRPα signaling in the course of the senescence and clearance of human red blood cells（RBCs）,the expression of CD47 on the membrane of RBCs stored at 4 ℃ or 37 ℃ in vitro and in vivo was detected by means of Western blot assay.The monocyte monolayer assay（MMA） was used to determine the difference of phagocytosis of THP-1 cells to RBCs with different ages（young or aged RBCs） and RBCs blocked with F（ab＇）2 fragments of anti-CD47 monoclonal antibody.In addition,Western blot assay was also applied to detect the expression of SIRPα phosphorylation on THP-1 cells phagocytosing the different age RBCs.It was demonstrated that the expression of CD47 on the cell membrane of human RBCs was significantly reduced both in vivo and in vitro,and along with the prolongation of the storage time of cells,the maximal degree of CD47 expression reduction approached up to 82.64%（in 4 ℃）.Difference existed in phagocytosis of different age of RBCs,and the aged RBCs were easily phagocytosed by THP-1 cells with a phagocytic rate of 35.32%13.72%,while that of the young RBCs was 13.72%（n=7,P0.02）.Meanwhile,the phagocytic rates to the fresh RBCs and to F（ab＇）2 fragment of anti-CD47 monoclonal antibody were 2.22% and 31.51% respectively（n=7.P0.02）.Also,the amount of SIRPα phosphorylation on THP-1 cells was rather different after phagocytosis of RBCs with different ages.In comparison to the young RBCs the amount of SIRPα phosphorylation of the aged RBCs declined significantly to 57.12%.These results suggest that the CD47-SIRPα signaling might be a key mechanism in controlling the senescence and clearance of human red blood cells.

关 键 词：CD47 SIRPα 磷酸化 红细胞 老化与吞噬 

分 类 号：R392[医药卫生—免疫学]