Very late antigen-5 and leukocyte function-associated antigen-1 are critical for early stage hematopoietic progenitor cell homing

Interactions of adhesion molecules among hematopoietic progenitor cells (HPC), bone marrow microvascular endothelial cells (BMMEC), and stromal cells are critical for hematopoiesis. However, most of the identified HPC receptors mediate interactions between HPC and stromal cells in the extravascular space. In order to study the interaction between HPC and BMMEC in the early period of homing, we preincubated mouse bone marrow mononuclear cells with blocking monoclonal antibodies against very late antigen-4 (VLA-4), VLA-5, leukocyte function-associated antigen-1 (LFA-1), and L-selectin before transplantation into irradiated splenectomized mice. Colony-forming units of granulocyte-macrophage (CFU-GM) seeding efficiency after preincubation with anti-VLA-5 resulted in a 54%, 67%, and 65% reduction, while that after preincubation with anti-LFA-1 resulted in a 37%, 25%, and 56% reduction, as compared with control, at 0.5, 2, and 24 h following transplantation, respectively. Similarly, the seeding efficiency was reduced by 12%, 13%, and 71% after preincubation with anti-VLA-4, and by -1%, 0%, and 18% after preincubation with anti-L-selectin. Thus, antibody blockade of VLA-5 and LFA-1 on HPC caused a significant decrease in CFU-GM seeding efficiency in the early period of homing. These observations suggest that VLA-5 and LFA-1 may play an important role in the recognition of BMMEC by HPC.