Hematopoietic Stem Cells Are Uniquely Selective in Their Migratory Response to Chemokines

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2002 May 8

PMID 11994419

Citations 159

Authors

Douglas E Wright

Edward P Bowman

Amy J Wagers

Eugene C Butcher

Irving L Weissman

Affiliations

Soon will be listed here.

Abstract

Although hematopoietic stem cell (HSC) migration into and out of sites of active hematopoiesis is poorly understood, it is a critical process that underlies modern clinical stem cell transplantation and may be important for normal hematopoietic homeostasis. Given the established roles of chemotactic cytokine (chemokine)-directed migration of other leukocyte subsets, the migration of murine HSC to a large panel of CC and CXC chemokines was investigated. HSC migrated only in response to stromal derived factor-1alpha, the ligand for the CXC chemokine receptor 4 (CXCR4). CXCR4 expression by HSC was confirmed by reverse transcription polymerase chain reaction analysis. Surprisingly, HSC also expressed mRNA for CCR3 and CCR9, although they failed to migrate to the ligands for these receptors. The sharply restricted chemotactic responsiveness of HSC is unique among leukocytes and may be necessary for the specific homing of circulating HSC to bone marrow, as well as for the maintenance of HSC in hematopoietic microenvironments.

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References

Lagasse E, CONNORS H, Reitsma M, Dohse M, Osborne L, Wang X . Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med. 2000; 6(11):1229-34. DOI: 10.1038/81326. View

Baum C, Weissman I, Tsukamoto A, Buckle A, Peault B . Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci U S A. 1992; 89(7):2804-8. PMC: 48751. DOI: 10.1073/pnas.89.7.2804. View

Wright D, Cheshier S, Wagers A, Randall T, Christensen J, Weissman I . Cyclophosphamide/granulocyte colony-stimulating factor causes selective mobilization of bone marrow hematopoietic stem cells into the blood after M phase of the cell cycle. Blood. 2001; 97(8):2278-85. DOI: 10.1182/blood.v97.8.2278. View

Shen H, Cheng T, Olszak I, Garcia-Zepeda E, Lu Z, Herrmann S . CXCR-4 desensitization is associated with tissue localization of hemopoietic progenitor cells. J Immunol. 2001; 166(8):5027-33. DOI: 10.4049/jimmunol.166.8.5027. View

Krause D, Theise N, Collector M, Henegariu O, Hwang S, Gardner R . Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 2001; 105(3):369-77. DOI: 10.1016/s0092-8674(01)00328-2. View

Wurbel M, Malissen M, Meffre E, Nussenzweig M, Richelme M, Carrier A . Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes. Blood. 2001; 98(9):2626-32. DOI: 10.1182/blood.v98.9.2626. View

Wright D, Wagers A, Gulati A, Johnson F, Weissman I . Physiological migration of hematopoietic stem and progenitor cells. Science. 2001; 294(5548):1933-6. DOI: 10.1126/science.1064081. View

Micklem H, Clarke C, Evans E, Ford C . Fate of chromosome-marked mouse bone marrow cells tranfused into normal syngeneic recipients. Transplantation. 1968; 6(2):299-302. View

Takada A, Takada Y, AMBRUS J . Proliferation of donor spleen and bone-marrow cells in the spleens and bone marrows of unirradiated and irradiated adult mice. Proc Soc Exp Biol Med. 1971; 136(1):222-6. DOI: 10.3181/00379727-136-35231. View

10.

Takada Y, Takada A . Proliferation of donor hematopoietic cells in irradiated and unirradiated host mice. Transplantation. 1971; 12(4):334-8. DOI: 10.1097/00007890-197110000-00021. View

11.

BRECHER G, Ansell J, Micklem H, Tjio J, CRONKITE E . Special proliferative sites are not needed for seeding and proliferation of transfused bone marrow cells in normal syngeneic mice. Proc Natl Acad Sci U S A. 1982; 79(16):5085-7. PMC: 346832. DOI: 10.1073/pnas.79.16.5085. View

12.

Bhatia M, Wang J, Kapp U, Bonnet D, Dick J . Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A. 1997; 94(10):5320-5. PMC: 24676. DOI: 10.1073/pnas.94.10.5320. View

13.

Fleming W, Alpern E, Uchida N, Ikuta K, Weissman I . Steel factor influences the distribution and activity of murine hematopoietic stem cells in vivo. Proc Natl Acad Sci U S A. 1993; 90(8):3760-4. PMC: 46381. DOI: 10.1073/pnas.90.8.3760. View

14.

Papayannopoulou T, Nakamoto B . Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin. Proc Natl Acad Sci U S A. 1993; 90(20):9374-8. PMC: 47570. DOI: 10.1073/pnas.90.20.9374. View

15.

Forster R, Emrich T, Kremmer E, Lipp M . Expression of the G-protein--coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells. Blood. 1994; 84(3):830-40. View

16.

Laterveer L, Lindley I, Hamilton M, Willemze R, Fibbe W . Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability. Blood. 1995; 85(8):2269-75. View

17.

Morrison S, Weissman I . The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity. 1994; 1(8):661-73. DOI: 10.1016/1074-7613(94)90037-x. View

18.

Papayannopoulou T, Craddock C, Nakamoto B, Priestley G, WOLF N . The VLA4/VCAM-1 adhesion pathway defines contrasting mechanisms of lodgement of transplanted murine hemopoietic progenitors between bone marrow and spleen. Proc Natl Acad Sci U S A. 1995; 92(21):9647-51. PMC: 40859. DOI: 10.1073/pnas.92.21.9647. View

19.

Laterveer L, Lindley I, Heemskerk D, Camps J, Pauwels E, Willemze R . Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8. Blood. 1996; 87(2):781-8. View

20.

Butcher E, Picker L . Lymphocyte homing and homeostasis. Science. 1996; 272(5258):60-6. DOI: 10.1126/science.272.5258.60. View