This is a first author paper of mine where, along with Dooyoung Lee and Dan Hammer, I studied how the relative densities of E-selectin and ICAM-1 affect the different steps of the leukocyte adhesion cascade. This cascade canonically consists of tethering, rolling, firm arrest, and transmigration. Using a recombinant protein surface, we could observe the first three steps in a highly controlled environment with specified densities. Thus, we could experimentally probe predictions made previously in the Hammer lab regarding synergy between selectins and adhesion molecules. In this case, we saw that optimal levels of firm arrest occurred on surfaces containing equimolar amounts of E-selectin and ICAM-1 or surfaces containing a 10X molar excess of ICAM-1. However, these surfaces required a certain level of ligand density (O(10^2) sites/µm^2), below which cells were unable to roll or arrest on the surface. Surfaces containing only one of the ligands were much less efficient at recruiting cells from the free stream compared to surfaces with both E-selectin and ICAM-1. Finally, we also showed almost no change in rolling velocity or time to stop on any of the surfaces, suggesting that the T cells control this aspect of the adhesion cascade independently of the adhesive surface.
Read this article on SpringerLink!
DOI: 10.1007/s12195-018-0519-x
Nicholas R. Anderson 