Beta1 integrins: zip codes and signaling relay for blood cells.
At least eight of the twelve known members of the beta1 integrin family are expressed on hematopoietic cells. Among these, the VCAM-1 receptor alpha4beta1 has received most attention as a main factor mediating firm adhesion to the endothelium during blood cell extravasation. Therapeutic trials are ongoing into the use of antibodies and small molecule inhibitors to target this interaction and hence obtain anti-inflammatory effects. However, extravasation is only one possible process that is mediated by beta1 integrins and there is evidence that they also mediate leukocyte retention and positioning in the tissue, lymphocyte activation and possibly migration within the interstitium. Genetic mouse models where integrins are selectively deleted on blood cells have been used to investigate these functions and further studies will be invaluable to critically evaluate therapeutic trials.
Sixt
Michael
M
Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
Bauer
Martina
M
Lämmermann
Tim
T
Fässler
Reinhard
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D039041:Integrin alpha4beta1; D019012:Integrin beta1