The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

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

På svenska

Author

  • Hong Qian
  • Karl Tryggvason
  • Sten Eirik W Jacobsen
  • Marja Ekblom

Summary, in English

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.

Department/s

Publishing year

2006

Language

English

Pages

3503-3510

Publication/Series

Blood

Volume

107

Issue

Jan 26

Document type

Journal article

Publisher

American Society of Hematology

Topic

  • Hematology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1528-0020