The chemokine SDF-1 is a chemoattractant for human CD34(+) hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34(+) progenitors to peripheral blood

被引:1129
作者
Aiuti, A
Webb, IJ
Bleul, C
Springer, T
GutierrezRamos, JC
机构
[1] MULLENIUM PHARMACEUT INC, CAMBRIDGE, MA 02139 USA
[2] CTR BLOOD RES INC, BOSTON, MA 02115 USA
[3] HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA
[4] HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA
[5] HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA
[6] DANA FARBER CANC INST, BLOOD COMPONENT LAB, BOSTON, MA 02115 USA
关键词
D O I
10.1084/jem.185.1.111
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first chemoattractant reported for human CD34(+) progenitor cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34(+) cells. SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34(+) cells is mediated by seven transmembrane receptors coupled to G(i) proteins. CD34(+) cells migrating to SDF-1 include cells with a more primitive (CD34(+)/CD38(-) or CD34(+)/DR(-)) phenotype as well as CD34(+) cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors. Chemotaxis of CD34(+) cells in response to SDF-1 is increased by IL-3 in vitro and is lower in CD34(+) progenitors from peripheral blood than in CD34(+) progenitors from bone marrow, suggesting that an altered response to SDF-1 may be associated with CD34 progenitor mobilization.
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页码:111 / 120
页数:10
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