|
|
 Previous Article | Table of Contents | Next Article 
RAPID COMMUNICATION
Kinetics of Central Nervous System Microglial and Macrophage Engraftment: Analysis Using a Transgenic Bone Marrow Transplantation Model
David W. Kennedy and
Janis L. Abkowitz
From the Division of Hematology, University of Washington, Seattle.
To determine the kinetics of tissue macrophage and microglial engraftment after bone marrow (BM) transplantation, we have developed a model using the ROSA 26 mouse. Transplanted ROSA 26 cells can be precisely identified in recipient animals because they constitutively express  -galactosidase (-gal) and neomycin resistance. B6/129 F2 mice were irradiated and transplanted with BM from ROSA 26 donors and their tissues (spleen, marrow, brain, liver, and lung) examined at various time points to determine the kinetics of engraftment. Frozen sections from transplanted animals were stained histochemically for -gal to identify donor cells. At 1, 2, 6, and 12 months posttransplantation, 98% to 100% of granulocyte-macrophage colonies were of donor (ROSA 26) origin determined by -gal staining and by neomycin resistance. Splenic monocytes/macrophages were 89% donor origin by 1 month confirming quick and complete engraftment of hematopoietic tissues. At this time, only rare ROSA 26 tissue macrophages or microglia were observed. Alveolar macrophage engraftment was evident by 2 months and had increased to 61% of total tissue macrophages at 1 year posttransplantation. The kinetics of liver Kupffer cell engraftment were similar to those seen in the lung. However, donor microglial engraftment remained only 23% of total microglia at 6 months and increased to only 30% by 1 year. Also, donor microglia were predominantly seen at perivascular and leptomeningeal, and not parenchymal, sites. The data show that microglia derive from BM precursors but turn over at a significantly slower rate than other tissue macrophages. No clinical or histological graft-versus-host disease was observed in the recipients of ROSA 26 BM. These kinetics may impact strategies for the gene therapy of lysosomal storage diseases. Because individual donor cells can be identified in situ, the ROSA 26 model should have many applications in transplantation biology including studies of homing and differentiation.
Blood, Vol. 90 No. 3 (August 1), 1997:
pp. 986-993
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Fukuda, M. Sata, N. Ishizaka, and R. Nagai
Critical Role of Bone Marrow Angiotensin II Type 1 Receptor in the Pathogenesis of Atherosclerosis in Apolipoprotein E Deficient Mice
Arterioscler. Thromb. Vasc. Biol.,
January 1, 2008;
28(1):
90 - 96.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Klein, J. C. Cornejo, N. K. Polakos, B. John, S. A. Wuensch, D. J. Topham, R. H. Pierce, and I. N. Crispe
Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages
Blood,
December 1, 2007;
110(12):
4077 - 4085.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. E. Wisse, K. Ogimoto, J. Tang, M. K. Harris Jr., E. W. Raines, and M. W. Schwartz
Evidence that Lipopolysaccharide-Induced Anorexia Depends upon Central, Rather than Peripheral, Inflammatory Signals
Endocrinology,
November 1, 2007;
148(11):
5230 - 5237.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wirenfeldt, L. Dissing-Olesen, A. Anne Babcock, M. Nielsen, M. Meldgaard, J. Zimmer, I. Azcoitia, R. G. Q. Leslie, F. Dagnaes-Hansen, and B. Finsen
Population Control of Resident and Immigrant Microglia by Mitosis and Apoptosis
Am. J. Pathol.,
August 1, 2007;
171(2):
617 - 631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Langmann
Microglia activation in retinal degeneration
J. Leukoc. Biol.,
June 1, 2007;
81(6):
1345 - 1351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Davoust, C. Vuaillat, G. Cavillon, C. Domenget, E. Hatterer, A. Bernard, C. Dumontel, P. Jurdic, C. Malcus, C. Confavreux, et al.
Bone marrow CD34+/B220+ progenitors target the inflamed brain and display in vitro differentiation potential toward microglia
FASEB J,
October 1, 2006;
20(12):
2081 - 2092.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. A. Maus, S. Janzen, G. Wall, M. Srivastava, T. S. Blackwell, J. W. Christman, W. Seeger, T. Welte, and J. Lohmeyer
Resident Alveolar Macrophages Are Replaced by Recruited Monocytes in Response to Endotoxin-Induced Lung Inflammation
Am. J. Respir. Cell Mol. Biol.,
August 1, 2006;
35(2):
227 - 235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Shi, T. Kazui, X. Jiang, N. Washiyama, K. Yamashita, H. Terada, and A. H. M. Bashar
Intrathecal Injection of Bone Marrow Stromal Cells Attenuates Neurologic Injury After Spinal Cord Ischemia
Ann. Thorac. Surg.,
June 1, 2006;
81(6):
2227 - 2234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chen, A. Larochelle, S. Fricker, G. Bridger, C. E. Dunbar, and J. L. Abkowitz
Mobilization as a preparative regimen for hematopoietic stem cell transplantation
Blood,
May 1, 2006;
107(9):
3764 - 3771.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-K. Kim, X. Alvarez, J. Fisher, B. Bronfin, S. Westmoreland, J. McLaurin, and K. Williams
CD163 Identifies Perivascular Macrophages in Normal and Viral Encephalitic Brains and Potential Precursors to Perivascular Macrophages in Blood
Am. J. Pathol.,
March 1, 2006;
168(3):
822 - 834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Desnues, M. Ihrig, D. Raoult, and J.-L. Mege
Whipple's Disease: a Macrophage Disease
Clin. Vaccine Immunol.,
February 1, 2006;
13(2):
170 - 178.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Landazuri and W. R. Taylor
The stem cell shell game. Focus on "The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture"
Am J Physiol Cell Physiol,
December 1, 2005;
289(6):
C1361 - C1362.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Xu, A. Manivannan, R. Dawson, I. J. Crane, M. Mack, P. Sharp, and J. Liversidge
Differentiation to the CCR2+ Inflammatory Phenotype In Vivo Is a Constitutive, Time-Limited Property of Blood Monocytes and Is Independent of Local Inflammatory Mediators
J. Immunol.,
November 15, 2005;
175(10):
6915 - 6923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Makui, R. J. Soares, W. Jiang, M. Constante, and M. M. Santos
Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading
Blood,
September 15, 2005;
106(6):
2189 - 2195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Brown, S. Gartner, T. Kawano, N. Benoit, and C. Cheng-Mayer
HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus
J. Leukoc. Biol.,
September 1, 2005;
78(3):
675 - 685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bradshaw, A. Gutierrez, J. H. Miyake, K. R. Davis, A. C. Li, C. K. Glass, L. K. Curtiss, and R. A. Davis
Facilitated replacement of Kupffer cells expressing a paraoxonase-1 transgene is essential for ameliorating atherosclerosis in mice
PNAS,
August 2, 2005;
102(31):
11029 - 11034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T A Albini, R C Wang, B Reiser, E Zamir, G S Wu, and N A Rao
Microglial stability and repopulation in the retina
Br. J. Ophthalmol.,
July 1, 2005;
89(7):
901 - 903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. I. Weinberg
Early Use of Drastic Therapy
N. Engl. J. Med.,
May 19, 2005;
352(20):
2124 - 2126.
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Matzner, E. Herbst, K. K. Hedayati, R. Lullmann-Rauch, C. Wessig, S. Schroder, C. Eistrup, C. Moller, J. Fogh, and V. Gieselmann
Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy
Hum. Mol. Genet.,
May 1, 2005;
14(9):
1139 - 1152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Everhart, W. Han, K. S. Parman, V. V. Polosukhin, H. Zeng, R. T. Sadikot, B. Li, F. E. Yull, J. W. Christman, and T. S. Blackwell
Intratracheal administration of liposomal clodronate accelerates alveolar macrophage reconstitution following fetal liver transplantation
J. Leukoc. Biol.,
February 1, 2005;
77(2):
173 - 180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Khmelewski, A. Becker, T. Meinertz, and W. D. Ito
Tissue Resident Cells Play a Dominant Role in Arteriogenesis and Concomitant Macrophage Accumulation
Circ. Res.,
September 17, 2004;
95(6):
e56 - e64.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Stout and J. Suttles
Functional plasticity of macrophages: reversible adaptation to changing microenvironments
J. Leukoc. Biol.,
September 1, 2004;
76(3):
509 - 513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. N. Hudson Keenihan and S. A. Robertson
Diversity in Phenotype and Steroid Hormone Dependence in Dendritic Cellsand Macrophages in the Mouse Uterus
Biol Reprod,
June 1, 2004;
70(6):
1562 - 1572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Asheuer, F. Pflumio, S. Benhamida, A. Dubart-Kupperschmitt, F. Fouquet, Y. Imai, P. Aubourg, and N. Cartier
Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein
PNAS,
March 9, 2004;
101(10):
3557 - 3562.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-C. Alves-Guerra, S. Rousset, C. Pecqueur, Z. Mallat, J. Blanc, A. Tedgui, F. Bouillaud, A.-M. Cassard-Doulcier, D. Ricquier, and B. Miroux
Bone Marrow Transplantation Reveals the in Vivo Expression of the Mitochondrial Uncoupling Protein 2 in Immune and Nonimmune Cells during Inflammation
J. Biol. Chem.,
October 24, 2003;
278(43):
42307 - 42312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Gieselmann
Metachromatic Leukodystrophy: Recent Research Developments
J Child Neurol,
September 1, 2003;
18(9):
591 - 594.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. L. Abkowitz, A. E. Robinson, S. Kale, M. W. Long, and J. Chen
Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure
Blood,
August 15, 2003;
102(4):
1249 - 1253.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Weimann, C. A. Charlton, T. R. Brazelton, R. C. Hackman, and H. M. Blau
Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains
PNAS,
February 18, 2003;
100(4):
2088 - 2093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schumann, K. Muhlen, A. K. Kiemer, A. M. Vollmar, and G. Tiegs
Parenchymal, But Not Leukocyte, TNF Receptor 2 Mediates T Cell-Dependent Hepatitis in Mice
J. Immunol.,
February 15, 2003;
170(4):
2129 - 2137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Rao, T. Kimoto, E. Zamir, R. Giri, R. Wang, S. Ito, G. Pararajasegaram, R. W. Read, and G.-S. Wu
Pathogenic Role of Retinal Microglia in Experimental Uveoretinitis
Invest. Ophthalmol. Vis. Sci.,
January 1, 2003;
44(1):
22 - 31.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, W. D. Shlomchik, G. Joe, J.-P. Louboutin, J. Zhu, A. Rivera, D. Giannola, and S. G. Emerson
APCs in the Liver and Spleen Recruit Activated Allogeneic CD8+ T Cells to Elicit Hepatic Graft-Versus-Host Disease
J. Immunol.,
December 15, 2002;
169(12):
7111 - 7118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Hume, I. L. Ross, S. R. Himes, R. T. Sasmono, C. A. Wells, and T. Ravasi
The mononuclear phagocyte system revisited
J. Leukoc. Biol.,
October 1, 2002;
72(4):
621 - 627.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ito, A. Suzuki, E. Imai, M. Okabe, and M. Hori
Bone Marrow Is a Reservoir of Repopulating Mesangial Cells during Glomerular Remodeling
J. Am. Soc. Nephrol.,
December 1, 2001;
12(12):
2625 - 2635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chen, Y. Li, L. Wang, Z. Zhang, D. Lu, M. Lu, and M. Chopp
Therapeutic Benefit of Intravenous Administration of Bone Marrow Stromal Cells After Cerebral Ischemia in Rats
Stroke,
April 1, 2001;
32(4):
1005 - 1011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W. Soper, M. D. Lessard, C. A. Vogler, B. Levy, W. G. Beamer, W. S. Sly, and J. E. Barker
Nonablative neonatal marrow transplantation attenuates functional and physical defects of {beta}-glucuronidase deficiency
Blood,
March 1, 2001;
97(5):
1498 - 1504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Wada, C. J. Tifft, and R. L. Proia
Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation
PNAS,
September 26, 2000;
97(20):
10954 - 10959.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Freeman, M. S. Roberts, C. A. Vogler, A. Nicholes, A. A. Hofling, and M. S. Sands
Behavior and Therapeutic Efficacy of beta -Glucuronidase-Positive Mononuclear Phagocytes in a Murine Model of Mucopolysaccharidosis Type VII
Blood,
September 15, 1999;
94(6):
2142 - 2150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Lichanska, C. M. Browne, G. W. Henkel, K. M. Murphy, M. C. Ostrowski, S. R. McKercher, R. A. Maki, and D. A. Hume
Differentiation of the Mononuclear Phagocyte System During Mouse Embryogenesis: The Role of Transcription Factor PU.1
Blood,
July 1, 1999;
94(1):
127 - 138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. N. Hahn, M. del Pilar Martin, X.-Y. Zhou, L. W. Mann, and A. d'Azzo
Correction of murine galactosialidosis by bone marrow-derived macrophages overexpressing human protective protein/cathepsin A under control of the colony-stimulating factor-1 receptor promoter
PNAS,
December 8, 1998;
95(25):
14880 - 14885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Kennedy and J. L. Abkowitz
Mature monocytic cells enter tissues and engraft
PNAS,
December 8, 1998;
95(25):
14944 - 14949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kyttala, O. Heinonen, L. Peltonen, and A. Jalanko
Expression and Endocytosis of Lysosomal Aspartylglucosaminidase in Mouse Primary Neurons
J. Neurosci.,
October 1, 1998;
18(19):
7750 - 7756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Swift, M. H. Farkas, A. S. Major, K. Valyi-Nagy, M. F. Linton, and S. Fazio
A Recycling Pathway for Resecretion of Internalized Apolipoprotein E in Liver Cells
J. Biol. Chem.,
June 15, 2001;
276(25):
22965 - 22970.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
