G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4

被引：1066

作者：

Petit, I

Szyper-Kravitz, M

Nagler, A

Lahav, M

Peled, A

Habler, L

Ponomaryov, T

Taichman, RS

Arenzana-Seisdedos, F

Fujii, N

Sandbank, J

Zipori, D

Lapidot, T ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

[3] Meir Med Ctr, Kefar Sava, Israel

[4] Sheba Med Ctr, Tel Hashomer, Israel

[5] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel

[6] Assaf Harofeh Med Ctr, IL-70300 Zerifin, Israel

[7] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA

[8] Inst Pasteur, Unite Immunol Virale, Paris, France

[9] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto, Japan

来源：

NATURE IMMUNOLOGY | 2002年 / 3卷 / 07期

基金：

以色列科学基金会;

关键词：

D O I：

10.1038/ni813

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Granulocyte colony-stimulating factor (G-CSF)-induced hematopoietic stem cell mobilization is widely used for clinical transplantation; however, the mechanism is poorly understood. We report here that G-CSF induced a reduction of the chemokine stromal cell-derived factor 1 (SDF-1) and an increase in its receptor CXCR4 in the bone marrow (BM), whereas their protein expression in the blood was less affected. The gradual decrease of BM SDF-1, due mostly to its degradation by neutrophil elastase, correlated with stem cell mobilization. Elastase inhibition reduced both activities. Human and murine stem cell mobilization was inhibited by neutralizing CXCR4 or SDF-1 antibodies, demonstrating SDF-1-CXCR4 signaling in cell egress. We suggest that manipulation of SDF-1-CXCR4 interactions may be a means with which to control the navigation of progenitors between the BM and blood to improve the outcome of clinical stem cell transplantation.

引用

页码：687 / 694

页数：8

共 65 条

[1] 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 [J].