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Distinct roles of integrins {alpha}6 and {alpha}4 in homing of fetal liver hematopoietic stem and progenitor cells.

Qian, Hong LU ; Georges-Labouesse, Elisabeth; Nyström, Alexander LU ; Domogatskaya, Anna; Tryggvason, Karl; Jacobsen, Sten Eirik W LU and Ekblom, Marja LU (2007) In Blood 110(7). p.2399-2407
Abstract
Homing of hematopoietic stem cells (HSCs) into the bone marrow (BM) is a prerequisite for establishment of hematopoiesis during development and following transplantation. However, the molecular interactions that control homing of HSCs, in particular, of fetal HSCs, are not well understood. Herein, we studied the role of the alpha 6 and alpha A integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hernatopoietic progenitor cells (HPCs) to adult BM by using integrin alpha 6 gene-deleted mice and functionblocking antibodies. Both integrins were ubiquitously expressed in FL Lin(-)Sca1 (+)Kit(+) (LSK) cells. Deletion of integrin alpha 6 receptor or inhibition by a functionblocking antibody inhibited FL LSK cell adhesion to... (More)
Homing of hematopoietic stem cells (HSCs) into the bone marrow (BM) is a prerequisite for establishment of hematopoiesis during development and following transplantation. However, the molecular interactions that control homing of HSCs, in particular, of fetal HSCs, are not well understood. Herein, we studied the role of the alpha 6 and alpha A integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hernatopoietic progenitor cells (HPCs) to adult BM by using integrin alpha 6 gene-deleted mice and functionblocking antibodies. Both integrins were ubiquitously expressed in FL Lin(-)Sca1 (+)Kit(+) (LSK) cells. Deletion of integrin alpha 6 receptor or inhibition by a functionblocking antibody inhibited FL LSK cell adhesion to its extracellular ligands, laminins-411 and -511 in vitro, and significantly reduced homing of HPCs to BM. In contrast, the anti-integrin alpha 6 antibody did not inhibit BM homing of HSCs. In agreement with this, integrin alpha 6 gene-deleted FL HSCs did not display any homing or engraftment defect compared with wildtype littermates. In contrast, inhibition of integrin alpha 4 receptor by a functionblocking antibody virtually abrogated homing of both FL HSCs and HPCs to BM, indicating distinct functions for integrin alpha 6 and alpha 4 receptors during homing of fetal HSCs and HPCs. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
110
issue
7
pages
2399 - 2407
publisher
American Society of Hematology
external identifiers
  • wos:000249800900036
  • scopus:34948887218
ISSN
1528-0020
DOI
10.1182/blood-2006-10-051276
language
English
LU publication?
yes
id
d6748f55-d1b1-442b-b2dc-f0a9a40a99e0 (old id 539604)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17586725&dopt=Abstract
date added to LUP
2007-12-20 08:17:03
date last changed
2017-10-01 03:58:43
@article{d6748f55-d1b1-442b-b2dc-f0a9a40a99e0,
  abstract     = {Homing of hematopoietic stem cells (HSCs) into the bone marrow (BM) is a prerequisite for establishment of hematopoiesis during development and following transplantation. However, the molecular interactions that control homing of HSCs, in particular, of fetal HSCs, are not well understood. Herein, we studied the role of the alpha 6 and alpha A integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hernatopoietic progenitor cells (HPCs) to adult BM by using integrin alpha 6 gene-deleted mice and functionblocking antibodies. Both integrins were ubiquitously expressed in FL Lin(-)Sca1 (+)Kit(+) (LSK) cells. Deletion of integrin alpha 6 receptor or inhibition by a functionblocking antibody inhibited FL LSK cell adhesion to its extracellular ligands, laminins-411 and -511 in vitro, and significantly reduced homing of HPCs to BM. In contrast, the anti-integrin alpha 6 antibody did not inhibit BM homing of HSCs. In agreement with this, integrin alpha 6 gene-deleted FL HSCs did not display any homing or engraftment defect compared with wildtype littermates. In contrast, inhibition of integrin alpha 4 receptor by a functionblocking antibody virtually abrogated homing of both FL HSCs and HPCs to BM, indicating distinct functions for integrin alpha 6 and alpha 4 receptors during homing of fetal HSCs and HPCs.},
  author       = {Qian, Hong and Georges-Labouesse, Elisabeth and Nyström, Alexander and Domogatskaya, Anna and Tryggvason, Karl and Jacobsen, Sten Eirik W and Ekblom, Marja},
  issn         = {1528-0020},
  language     = {eng},
  number       = {7},
  pages        = {2399--2407},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Distinct roles of integrins {alpha}6 and {alpha}4 in homing of fetal liver hematopoietic stem and progenitor cells.},
  url          = {http://dx.doi.org/10.1182/blood-2006-10-051276},
  volume       = {110},
  year         = {2007},
}