Migration against the direction of flow is LFA-1-dependent in human hematopoietic stem and progenitor cells.
The recruitment of immune cells during inflammation is regulated by a multi-step cascade of cell rolling, activation, adhesion and transmigration through the endothelial barrier. Similarly, hematopoietic stem and progenitor cells (HSPCs) use this pathway to migrate and home to the bone marrow. After selectin-mediated braking, HSPCs migrate on adhesion ligands presented by the vascular endothelium including ICAM-1, VCAM-1 or MAdCAM-1. Here, we report that both the KG1a stem cell line and primary bone marrow CD34+ HSPCs can migrate against the direction of fluid flow on surfaces coated with cell adhesion molecules (CAMs), a behavior thus far only reported in T lymphocytes. We demonstrate that KG1a cells and primary HSPCs migrate upstream on surfaces presenting ICAM-1, downstream on surfaces presenting VCAM-1, and both upstream and downstream on surfaces presenting MAdCAM-1. In addition, we demonstrate that KG1a cells and HSPCs display upstream migration both on surfaces with multiple CAMs, as well as on human umbilical vein endothelial cell (HUVEC) monolayers. By blocking with monoclonal antibodies, we show that lymphocyte function-associated antigen-1 (LFA-1) is the key receptor responsible for upstream migration on the endothelium during the trafficking of HSPCs to the bone marrow.This article has an associated First Person interview with the first author of the paper.
['Buffone|Alexander|A|', 'Anderson|Nicholas R|NR|', 'Hammer|Daniel A|DA|0000-0002-3522-3154']
D002448:Cell Adhesion D015815:Cell Adhesion Molecules D002460:Cell Line D002465:Cell Movement D002478:Cells, Cultured D004730:Endothelium, Vascular D018380:Hematopoietic Stem Cell Transplantation D006412:Hematopoietic Stem Cells D006801:Humans D007136:Immunoglobulins D018799:Intercellular Adhesion Molecule-1 D016169:Lymphocyte Function-Associated Antigen-1 D009088:Mucoproteins D019010:Vascular Cell Adhesion Molecule-1
Hematopoietic stem and progenitor cell Inflammation Homing Endothelium ICAM-1 VCAM-1 MAdCAM-1 LFA-1 Cell migration