CD47 Is Upregulated on Circulating Hematopoietic Stem Cells and Leukemia Cells to Avoid Phagocytosis

被引：1323

作者：

Jaiswal, Siddhartha ^{[1
,2
]}

Jamieson, Catriona H. M. ^{[3
]}

Pang, Wendy W. ^{[1
,2
]}

Park, Christopher Y. ^{[1
,2
]}

Chao, Mark P. ^{[1
,2
]}

Majeti, Ravindra ^{[1
,2
]}

Traver, David ^{[4
]}

van Rooijen, Nico ^{[5
]}

Weissman, Irving L. ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Ludwig Ctr Stanford, Stanford Canc Ctr,Dept Pathol, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[3] Univ Calif San Diego, Moores UCSD Canc Ctr, Stem Cell Res Program, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA

[5] Vrije Univ Amsterdam, VUMC, Dept Mol Cell Biol, Amsterdam, Netherlands

来源：

CELL | 2009年 / 138卷 / 02期

基金：

美国国家卫生研究院;

关键词：

INTEGRIN-ASSOCIATED PROTEIN; COLONY-STIMULATING FACTOR; MYELOID PROGENITORS; EXPRESSION; MOBILIZATION; BLOOD; ENGRAFTMENT; RECEPTOR; MARKER; MICE;

D O I：

10.1016/j.cell.2009.05.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Macrophages clear pathogens and damaged or aged cells from the blood stream via phagocytosis. Cell-surface CD47 interacts with its receptor on macrophages, SIRP alpha, to inhibit phagocytosis of normal, healthy cells. We find that mobilizing cytokines and inflammatory stimuli cause CD47 to be transiently upregulated on mouse hematopoietic stem cells (HSCs) and progenitors just prior to and during their migratory phase, and that the level of CD47 on these cells determines the probability that they are engulfed in vivo. CD47 is also constitutively upregulated on mouse and human myeloid leukemias, and overexpression of CD47 on a myeloid leukemia line increases its pathogenicity by allowing it to evade phagocytosis. We conclude that CD47 upregulation is an important mechanism that provides protection to normal HSCs during inflammation-mediated mobilization, and that leukemic progenitors co-opt this ability in order to evade macrophage killing.

引用

页码：271 / 285

页数：15

共 42 条

[1] A clonogenic common myeloid progenitor that gives rise to all myeloid lineages [J].