(271g) Migration Against the Direction of Flow Is LFA-1 Dependent in Human Hematopoietic Stem and Progenitor Cells
AIChE Annual Meeting
Tuesday, October 31, 2017 - 9:48am to 10:06am
Here we describe for the first time how both the KG1a immortalized 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). Using a laminar flow chamber, we demonstrate that KG1a cells and primary HSPCs migrate upstream on ICAM-1, downstream on VCAM-1, and both upstream and downstream on MAdCAM-1. Also, we demonstrate that KG1a cells and HSPCs display upstream migration on mixed surfaces of multiple CAMs and surfaces containing both E-selectin and CAMs, much like the activated endothelial surface. Furthermore, both KG1a and Primary HSPCs migrate upstream on activated HUVEC monolayers at shear rates seen in the vasculature. Blocking with monoclonal antibodies, we show that Lymphocyte Function-associated Antigen-1 (LFA-1) is the sole cell-borne integrin responsible for upstream migration along the endothelium. Signaling events downstream of LFA-1 (Î±LÎ²2) engagement are critical to this mode of motility and furthermore, the localization of activated LFA-1 and the F-actin network are fundamentally different during upstream as compared to downstream migration. In all, this upstream motility has direct implications in understanding of how HSPCs traffic during bone marrow transplants and holds potential in having HSPCs better home to the marrow.
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