Figure 1.
Figure 1. Dominant role of α4-integrin/VCAM-1 interaction in BM homing of fresh BM-HPCs. (A) AMD3100 or PTX block SDF-1-induced chemotaxis. Chemokinetic (▦) or chemotactic (SDF-1, ▪) migration of fresh c-kit+ WT BM-HPCs through 5-μm transwells was tested in untreated control BM cells, in the presence of AMD3100 (100 μg/mL) or after PTX treatment (100 ng/mL, 4 hours). AMD3100 (left) significantly attenuated SDF-1-directed migration. PTX incubation (right) completely blocked SDF-1-directed migration, but low-level spontaneous migration was maintained in the presence of PTX (*P < .05). (B-D) BM homing of fresh BM-HPCs was tested 3 hours (B) or 18 hours (C,D) after transplantation of lethally irradiated recipients. Donor-cell strain/treatment and recipient strain are indicated below the respective bars. BM homing is given as the percentage of injected CFU-Cs recovered per femur. Depicted are mean plus SEM of all mice tested with this modality. (B) Three-hour BM homing of fresh BM cells treated with or without AMD3100. BM homing of fresh WT BM cells was not affected by AMD3100 incubation/coinjection. BM homing of α4-/- BM cells in WT recipients was significantly decreased compared with WT-to-WT (*P < .05). AMD3100 treatment of α4-/- BM cells additionally reduced BM homing (*P < .05 compared with untreated α4-/--to-WT transplantation). (C) Eighteen-hour BM homing of fresh BM cells. BM homing of α4-/- cells in WT recipients, or WT cells in VCAM-1-/- recipients was significantly reduced compared with WT-to-WT (*P < .05). BM homing of WT BM in CD62-/- recipients, which are deficient in endothelial selectins, was no different from WT-to-WT. BM homing of α4-/- BM-HPCs in CD62-/- recipients was significantly less efficient than that of α4-/- in WT (*P < .05). (D) Eighteen-hour BM homing of fresh PTX-treated BM cells. BM homing of PTX-treated WT cells in WT recipients was no different from untreated WT-to-WT, but BM homing of PTX-treated α4-/- cells in WT recipients, or BM homing of PTX-treated WT cells in VCAM-1-/- hosts were almost completely abrogated (*P < .05 compared with untreated α4-/--to-WT or WT-to-VCAM-1 transplantation). In contrast, PTX-treated WT cells homed normally in CD62-/- hosts.

Dominant role of α4-integrin/VCAM-1 interaction in BM homing of fresh BM-HPCs. (A) AMD3100 or PTX block SDF-1-induced chemotaxis. Chemokinetic (▦) or chemotactic (SDF-1, ▪) migration of fresh c-kit+ WT BM-HPCs through 5-μm transwells was tested in untreated control BM cells, in the presence of AMD3100 (100 μg/mL) or after PTX treatment (100 ng/mL, 4 hours). AMD3100 (left) significantly attenuated SDF-1-directed migration. PTX incubation (right) completely blocked SDF-1-directed migration, but low-level spontaneous migration was maintained in the presence of PTX (*P < .05). (B-D) BM homing of fresh BM-HPCs was tested 3 hours (B) or 18 hours (C,D) after transplantation of lethally irradiated recipients. Donor-cell strain/treatment and recipient strain are indicated below the respective bars. BM homing is given as the percentage of injected CFU-Cs recovered per femur. Depicted are mean plus SEM of all mice tested with this modality. (B) Three-hour BM homing of fresh BM cells treated with or without AMD3100. BM homing of fresh WT BM cells was not affected by AMD3100 incubation/coinjection. BM homing of α4-/- BM cells in WT recipients was significantly decreased compared with WT-to-WT (*P < .05). AMD3100 treatment of α4-/- BM cells additionally reduced BM homing (*P < .05 compared with untreated α4-/--to-WT transplantation). (C) Eighteen-hour BM homing of fresh BM cells. BM homing of α4-/- cells in WT recipients, or WT cells in VCAM-1-/- recipients was significantly reduced compared with WT-to-WT (*P < .05). BM homing of WT BM in CD62-/- recipients, which are deficient in endothelial selectins, was no different from WT-to-WT. BM homing of α4-/- BM-HPCs in CD62-/- recipients was significantly less efficient than that of α4-/- in WT (*P < .05). (D) Eighteen-hour BM homing of fresh PTX-treated BM cells. BM homing of PTX-treated WT cells in WT recipients was no different from untreated WT-to-WT, but BM homing of PTX-treated α4-/- cells in WT recipients, or BM homing of PTX-treated WT cells in VCAM-1-/- hosts were almost completely abrogated (*P < .05 compared with untreated α4-/--to-WT or WT-to-VCAM-1 transplantation). In contrast, PTX-treated WT cells homed normally in CD62-/- hosts.

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