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Contribution of {alpha}6-integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with {alpha}4-integrins.

Qian, Hong LU ; Tryggvason, Karl ; Jacobsen, Sten Eirik W LU and Ekblom, Marja LU (2006) In Blood 107(Jan 26). p.3503-3510
Abstract
The laminin receptor integrin alpha 6 chain is ubiquitously expressed in human and mouse hematopoietic stem and progenitor cells. We have studied its role for homing of stem and progenitor cells to mouse hematopoietic tissues In vivo. A function-blocking anti-integrin alpha 6 antibody significantly reduced progenitor cell homing to bone marrow (BM) of lethally irradiated mice, with a corresponding retention of progenitors in blood. Remarkably, the anti-integrin alpha 6 antibody profoundly inhibited BM homing of long-term multilineage engrafting stem cells, studied by competitive repopulation assay and analysis of donor-derived lymphocytes and myeloid cells in blood 16 weeks after transplantation. A similar profound inhibition of long-term... (More)
The laminin receptor integrin alpha 6 chain is ubiquitously expressed in human and mouse hematopoietic stem and progenitor cells. We have studied its role for homing of stem and progenitor cells to mouse hematopoietic tissues In vivo. A function-blocking anti-integrin alpha 6 antibody significantly reduced progenitor cell homing to bone marrow (BM) of lethally irradiated mice, with a corresponding retention of progenitors in blood. Remarkably, the anti-integrin alpha 6 antibody profoundly inhibited BM homing of long-term multilineage engrafting stem cells, studied by competitive repopulation assay and analysis of donor-derived lymphocytes and myeloid cells in blood 16 weeks after transplantation. A similar profound inhibition of long-term stem cell homing was obtained by using a function-blocking antibody against alpha 4 integrin, studied in parallel. Furthermore, the anti-integrin alpha 6 and alpha 4 antibodies synergistically inhibited homing of short-term repopulating stem cells. Intravenous injection of anti-integrin alpha 6 antibodies, in contrast to antibodies against alpha 4 integrin, did not mobilize progenitors or enhance cytokine-induced mobilization by G-CSF. Our results provide the first evidence for a distinct functional role of integrin alpha 6 receptor during hematopoietic stem and progenitor cell homing and collaboration of alpha 6 integrin with alpha 4 integrin receptors during homing of short-term stem cells. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
107
issue
Jan 26
pages
3503 - 3510
publisher
American Society of Hematology
external identifiers
  • wos:000237217600029
  • pmid:16439681
  • scopus:33646392969
ISSN
1528-0020
DOI
10.1182/blood-2005-10-3932
language
English
LU publication?
yes
id
ab92f889-7da9-4749-b57f-3b9d9fdfaa9e (old id 150103)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16439681&dopt=Abstract
date added to LUP
2016-04-01 11:43:48
date last changed
2020-08-12 03:09:15
@article{ab92f889-7da9-4749-b57f-3b9d9fdfaa9e,
  abstract     = {The laminin receptor integrin alpha 6 chain is ubiquitously expressed in human and mouse hematopoietic stem and progenitor cells. We have studied its role for homing of stem and progenitor cells to mouse hematopoietic tissues In vivo. A function-blocking anti-integrin alpha 6 antibody significantly reduced progenitor cell homing to bone marrow (BM) of lethally irradiated mice, with a corresponding retention of progenitors in blood. Remarkably, the anti-integrin alpha 6 antibody profoundly inhibited BM homing of long-term multilineage engrafting stem cells, studied by competitive repopulation assay and analysis of donor-derived lymphocytes and myeloid cells in blood 16 weeks after transplantation. A similar profound inhibition of long-term stem cell homing was obtained by using a function-blocking antibody against alpha 4 integrin, studied in parallel. Furthermore, the anti-integrin alpha 6 and alpha 4 antibodies synergistically inhibited homing of short-term repopulating stem cells. Intravenous injection of anti-integrin alpha 6 antibodies, in contrast to antibodies against alpha 4 integrin, did not mobilize progenitors or enhance cytokine-induced mobilization by G-CSF. Our results provide the first evidence for a distinct functional role of integrin alpha 6 receptor during hematopoietic stem and progenitor cell homing and collaboration of alpha 6 integrin with alpha 4 integrin receptors during homing of short-term stem cells.},
  author       = {Qian, Hong and Tryggvason, Karl and Jacobsen, Sten Eirik W and Ekblom, Marja},
  issn         = {1528-0020},
  language     = {eng},
  number       = {Jan 26},
  pages        = {3503--3510},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Contribution of {alpha}6-integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with {alpha}4-integrins.},
  url          = {http://dx.doi.org/10.1182/blood-2005-10-3932},
  doi          = {10.1182/blood-2005-10-3932},
  volume       = {107},
  year         = {2006},
}