Dynamic contributions of P‐ and E‐selectins to β2‐integrin‐induced neutrophil transmigration

Leukocyte transendothelial migration is a key step in their recruitment to sites of inflammation. However, synergic regulation of endothelium-expressed selectins on leukocyte transmigration remains unclear. In this study, an in vitro model was developed to investigate the dynamic contributions of P- and E-selectin to polymorphonuclear neutrophil (PMN) transmigration under static conditions. Human umbilical vein endothelial cells (HUVECs) were treated with LPS for 4 or 12 h to induce different expression of selectins and intercellular adhesion molecule (ICAM)-1. PMN transmigration was increased significantly by LPS stimulation, which was higher on 4-h than on 12-h LPStreated HUVECs. Blocking and competitive tests indicated that P-selectin engages PSGL-1 to activate β2-integrin and initiate PMN transmigration within the first 15 min, whereas E-selectin engages CD44 to influence PMN transmigration after 15 min. P- and E-selectin–induced β2-integrin activation is likely conducted through the spleen tyrosine kinase signaling pathway. Complicated complementary and competitive mechanisms are involved in the interaction of P-/E-selectins and their ligands to promote PMN transmigration. These results provide direct evidence of the distinct and dynamic contribution of P- and E-selectins in mediating PMN transmigration and give new insight into PMN interaction with the vessel wall.—Gong, Y., Zhang, Y., Feng, S., Liu, X., Lü, S., Long, M. Dynamic contributions of P- and E-selectins to β2-integrin-induced neutrophil transmigration. FASEB J. 31, 212–223 (2017) www.fasebj.org