Transmigration of CD34+ progenitor and leukemic cells through bone marrow endothelial cells in vitro: effect of the chemokine SDF-1
Adhesion and transendothelial migration are crucial events involved in mobilization and homing of hematopoietic progenitor cells. We have shown that only a small fraction of peripheral blood CD34+ cells migrates through bone marrow endothelial cells in vitro. Recently, it has been demonstrated that the stroma-derived chemokine SDF-1 acts as a chemotactic factor for hematopoietic progenitor cells. We assessed the effect of SDF-1 on transendothelial migration of CD34+ progenitors and leukemic cell lines using confluent monolayers of the bone marrow endothelial cell line BMEC-1 grown on 3 urn microporous membranes. As a source of SDF- , conditioned medium of the cell line MS-5 was added to the lower chamber of the transmigration system resulting in a transendothelial SDF-1 gradient. Without addition of SDF- , only 1 1±0. 4 % (mean ±SEM) of peripheral blood CD34+ cells transmigrated within 10 h, in contrast to 20. 2+1. 7 % when SDF-1 was added. Furthermore, only CD34+/CD38++, committed progenitors migrated spontaneously, while a positive SDF-1 gradient resulted in migration of both CD34+/CD38- and CD34+/CD38+ cells. Spontaneous and SDF-1 induced transmigration was partially blocked by LFA-1 antibodies, whereas L-selectin and VLA-4 antibodies had no effect. Surprisingly, transendothelial migration of CD34+ leukemic KG] cells was not enhanced by SDF-1 (<0. 1 % with SDF-1 vs. <0. 1 % without), while the more mature CD34- HL60 cells migrated moderately in response to the chemokine (3. 8+0. 9 % with SDF-1 vs. <0. 1 % without). We conclude that a transendothelial SDF-1 gradient supports migration particularly of primitive CD34+ progenitors and may therefore play an important role in stem cell homing In addition, lack of response to SDF-1 could result in egress of leukemic CD34+ cells from the bone marrow into the circulation.