The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice

Hematopoietic stem cell homing and engraftment require several adhesion Int eractions, which are not fully understood. Engraftment of nonobese/severe c ombined immunodeficiency (NOD/SCID) mice by human stem cells is dependent o n the major integrins very late activation antigen-4 (VLA-4); VLA-5; and to a lesser degree, lymphocyte function associated antigen-1 (LFA-1). Treatme nt of human CD34(+) cells with antibodies to either VLA-4 or VLA-5 prevente d engraftment, and treatment with anti-LFA-l antibodies significantly reduc ed the levels of engraftment. Activation of CD34(+) cells, which bear the c hemokine receptor CXCR4, with stromal derived factor 1 (SDF-1) led to firm adhesion and transendothelial migration, which was dependent on LFA-1/ICAM- 1 (Intracellular adhesion molecule-1)and VLA-4/VCAM-1 (vascular adhesion mo lecule-1). Furthermore, SDF1-induced polarization and extravasation of CD34 (+)/CXCR4(+) cells through the extracellular matrix underlining the endothe lium was dependent on both VLA-4 and VLA-5. Our results demonstrate that re populating human stem cells functionally express LFA-1, VLA-4, and VLA-5, F urthermore, this study implies a novel approach to further advance clinical transplantation.(Blood. 2000;95:3289-3296) (C) 2000 by The American Societ y of Hematology.