|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1524-1533
Enhanced Myeloid Progenitor Cell Cycling and Apoptosis in Mice
Lacking the Chemokine Receptor, CCR2
Suzanna Reid,
Alec Ritchie,
Landin Boring,
Jennifa Gosling,
Scott Cooper,
Giao Hangoc,
Israel F. Charo, and
Hal E. Broxmeyer
From the Departments of Microbiology/Immunology and Medicine, and The
Walther Oncology Center, Indiana University School of Medicine,
Indianapolis, IN; The Walther Cancer Institute, Indianapolis, IN; the
Cardiovascular Research Institute, Gladstone Institute of
Cardiovascular Disease, and the Department of Medicine, University of
California, San Francisco, CA.
Chemokines regulate hematopoiesis in part by influencing the
proliferative status of myeloid progenitor cells (MPC). Human MCP-1/murine JE, a myelosuppressive chemokine, specifically binds C-C
chemokine receptor 2 (CCR2). Transgenic mice containing a targeted
disruption in CCR2 that prevents expression of CCR2 mRNA and protein
and have MPC that are insensitive to inhibition by MCP-1 and JE in
vitro were assessed for potential abnormalities in growth of bone
marrow (BM) and spleen MPC. MPC in both unseparated and
c-kit+lin populations of BM from
CCR2-deficient ( /) mice were in a greatly increased proliferation
state compared with CCR2 littermate control (+/+) mice, an effect
not apparent with progenitors from spleens of CCR2 (/) mice.
Increased cycling status of CCR2 (/) BM MPC did not result in
increased numbers of nucleated cells or MPC in BM or spleens of CCR2
(/) mice. Possible reasons for this apparent discrepancy were
highlighted by flow cytometric analysis of
c-kit+lin BM cells and colony formation by
MPC subjected to delayed addition of growth factors. The
c-kit+lin population of BM cells from CCR2
(/) mice had a significantly higher percentage of apoptotic cells
than those from CCR2 (+/+) BM. However, elevated apoptosis was not
associated with decreased numbers of
c-kit+lin cells. The increased percentage
of apoptotic c-kit+lin cells was due to
elevated apoptosis within the c-kitdimlin,
but not the c-kitbrightlin, subpopulations
of cells. Consistent with enhanced apoptosis of phenotypically defined
cells, MPC from CCR2 (/) BM and purified c-kit+lin cells demonstrated decreased
cell survival in vitro upon delayed addition of growth factors. The
data suggest that signals received by CCR2 limit proliferation of
progenitor cells in the BM, but also enhance survival of these cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. E. Broxmeyer, S. Sehra, S. Cooper, L. M. Toney, S. Kusam, J. J. Aloor, C. C. Marchal, M. C. Dinauer, and A. L. Dent
Aberrant Regulation of Hematopoiesis by T Cells in BAZF-Deficient Mice
Mol. Cell. Biol.,
August 1, 2007;
27(15):
5275 - 5285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. P. de Lema, H. Maier, T. J. Franz, M. Escribese, S. Chilla, S. Segerer, N. Camarasa, H. Schmid, B. Banas, S. Kalaydjiev, et al.
Chemokine Receptor Ccr2 Deficiency Reduces Renal Disease and Prolongs Survival in MRL/lpr Lupus-Prone Mice
J. Am. Soc. Nephrol.,
December 1, 2005;
16(12):
3592 - 3601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Rao, M. P. Quinones, E. Garavito, Y. Kalkonde, F. Jimenez, C. Gibbons, J. Perez, P. Melby, W. Kuziel, R. L. Reddick, et al.
CC Chemokine Receptor 2 Expression in Donor Cells Serves an Essential Role in Graft-versus-Host-Disease
J. Immunol.,
November 1, 2003;
171(9):
4875 - 4885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Broxmeyer, L. Kohli, C. H. Kim, Y. Lee, C. Mantel, S. Cooper, G. Hangoc, M. Shaheen, X. Li, and D. W. Clapp
Stromal cell-derived factor-1/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and G{alpha}i proteins and enhances engraftment of competitive, repopulating stem cells
J. Leukoc. Biol.,
May 1, 2003;
73(5):
630 - 638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Broxmeyer, S. Cooper, L. Kohli, G. Hangoc, Y. Lee, C. Mantel, D. W. Clapp, and C. H. Kim
Transgenic Expression of Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo
J. Immunol.,
January 1, 2003;
170(1):
421 - 429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Basu, G. Hodgson, M. Katz, and A. R. Dunn
Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation
Blood,
July 18, 2002;
100(3):
854 - 861.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Roque, W. J.H. Kim, M. Gazdoin, A. Malik, E. D. Reis, J. T. Fallon, J. J. Badimon, I. F. Charo, and M. B. Taubman
CCR2 Deficiency Decreases Intimal Hyperplasia After Arterial Injury
Arterioscler Thromb Vasc Biol,
April 1, 2002;
22(4):
554 - 559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhang, S. Fukuda, Y. Lee, G. Hangoc, S. Cooper, R. Spolski, W. J. Leonard, and H. E. Broxmeyer
Essential Role of Signal Transducer and Activator of Transcription (Stat)5a but Not Stat5b for Flt3-Dependent Signaling
J. Exp. Med.,
September 5, 2000;
192(5):
719 - 728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Murphy, M. Baggiolini, I. F. Charo, C. A. Hebert, R. Horuk, K. Matsushima, L. H. Miller, J. J. Oppenheim, and C. A. Power
International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors
Pharmacol. Rev.,
March 1, 2000;
52(1):
145 - 176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.D. Cashman, I. Clark-Lewis, A.C. Eaves, and C.J. Eaves
Differentiation Stage-Specific Regulation of Primitive Human Hematopoietic Progenitor Cycling by Exogenous and Endogenous Inhibitors in an In Vivo Model
Blood,
December 1, 1999;
94(11):
3722 - 3729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Broxmeyer, S. Cooper, G. Hangoc, J.-L. Gao, and P. M. Murphy
Dominant Myelopoietic Effector Functions Mediated by Chemokine Receptor CCR1
J. Exp. Med.,
June 21, 1999;
189(12):
1987 - 1992.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Roque, W. J.H. Kim, M. Gazdoin, A. Malik, E. D. Reis, J. T. Fallon, J. J. Badimon, I. F. Charo, and M. B. Taubman
CCR2 Deficiency Decreases Intimal Hyperplasia After Arterial Injury
Arterioscler Thromb Vasc Biol,
April 1, 2002;
22(4):
554 - 559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
