Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway

被引:116
作者
Richards, MK
Liu, FL
Iwasaki, H
Akashi, K
Link, DC
机构
[1] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA
[2] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
关键词
D O I
10.1182/blood-2003-02-0593
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Granulocyte colony-stimulating factor (G-CSF) is the principal cytokine regulating granulopoiesis. G-CSF receptor-deficient mice (G-CSFR-/-) are neutropenic but have only a modest reduction of committed myeloid progenitors. Since it is likely that compensatory mechanisms are induced by the severe neutropenia present in G-CSFR-/- mice, a competitive repopulation assay was performed. These data show that under basal conditions, G-CSF drives nearly all of granulopoiesis through multiple mechanisms. Most importantly, G-CSFR signals regulate the production and/or maintenance of committed-myeloid progenitors. Surprisingly, G-CSFR signals also play a significant role in the regulation of primitive multipotential progenitors in vivo. The contribution of G-CSFR-/- cells to the hematopoietic stem cell compartment is modestly reduced. Moreover, a marked decrease in the contribution of G-CSFR-/- cells to other progenitors in the myeloid pathway, including erythroid and megakaryocytic progenitors, is observed. In contrast, relative to the hematopoietic stem cell compartment, the contribution of G-CSFR-/- cells to the lymphoid lineages is increased. These data suggest that G-CSFR signals may play a role in directing the commitment of primitive hematopoietic progenitors to the common myeloid lineage. Thus, regulation of G-CSF levels may provide a mechanism for directing primitive hematopoietic progenitors into the common myeloid lineage in response to environmental stresses. (C) 2003 by The American Society of Hematology.
引用
收藏
页码:3562 / 3568
页数:7
相关论文
共 36 条
[1]   A clonogenic common myeloid progenitor that gives rise to all myeloid lineages [J].
Akashi, K ;
Traver, D ;
Miyamoto, T ;
Weissman, IL .
NATURE, 2000, 404 (6774) :193-197
[2]   Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice [J].
Akashi, K ;
Kondo, M ;
vonFreedenJeffry, U ;
Murray, R ;
Weissman, IL .
CELL, 1997, 89 (07) :1033-1041
[3]   Very late antigen-5 and leukocyte function-associated antigen-1 are critical for early stage hematopoietic progenitor cell homing [J].
Asaumi, N ;
Omoto, E ;
Mahmut, N ;
Katayama, Y ;
Takeda, K ;
Shinagawa, K ;
Harada, M .
ANNALS OF HEMATOLOGY, 2001, 80 (07) :387-392
[4]   Molecular analysis of the granulocyte colony-stimulating factor receptor [J].
Avalos, BR .
BLOOD, 1996, 88 (03) :761-777
[5]  
Basu S, 2000, BLOOD, V95, P3725
[6]   High frequency of long-term culture-initiating cells retain in vivo repopulation and self-renewal capacity [J].
Cho, RH ;
Müller-Sieburg, CE .
EXPERIMENTAL HEMATOLOGY, 2000, 28 (09) :1080-1086
[7]   EFFECT OF ERYTHROPOIETIN ON COLONIAL GROWTH OF ERYTHROID PRECURSOR CELLS INVITRO [J].
COOPER, MC ;
LEVY, J ;
CANTOR, LN ;
MARKS, PA ;
RIFKIND, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1974, 71 (05) :1677-1680
[8]  
DEMETRI GD, 1991, BLOOD, V78, P2791
[9]  
DORSHKIND K, 1986, J IMMUNOL, V136, P422
[10]   Exclusive expression of G-CSF receptor on myeloid progenitors in bone marrow CD34+ cells [J].
Ebihara, Y ;
Xu, MJ ;
Manabe, A ;
Kikuchi, A ;
Tanaka, R ;
Kato, S ;
Nakahata, T ;
Tsuji, K .
BRITISH JOURNAL OF HAEMATOLOGY, 2000, 109 (01) :153-161