Poster Presentation 2014 International Biophysics Congress

Dynamic contributions of E- and P-selectin in neutrophil transmigration (#621)

Yan Zhang 1 , Yixin Gong 1 , Xiaofeng Liu 1 , Shouqin Lu 1 , Mian Long 1
  1. Center of Biomechanics and Bioengineering and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China

Selectins and their ligands are required for leukocyte extravasation during inflammation. In the initial phase of the process, neutrophils (PMNs) first tether to and roll on P- and E-selectin expressed on activated endothelial cells via interacting with P-selectin glycoprotein ligand-1 (PSGL-1) for P-selectin and with PSGL-1, CD44, or E-selectin ligand-1 for E-selectin. Although the leukocyte–endothelial cell interactions have been extensively investigated, the dynamic contributions of the two selectin (P- and E-selectin) in mediating neutrophil transmigration is not clear.


To examine the potential involvement of these adhesion molecules in PMN transmigration, HUVEC is treated with LPS for 4 and 12 hours to get different selectin and ICAM-1 expression. P- or E-selectin expression of LPS-treated HUVECs is peaked by 4–5 h and return to baseline within 8–12 h. Preliminary data shows that PMN transmigration is significantly higher and faster in 4h-LPS stimulated HUVEC than those 12h-LPS treatment. Treatment with blocking and activating antibodies to the β2 integrins shows that high affinity LFA-1 binding to ICAM-1 is primarily responsible for mediating PMN transmigration across HUVEC. Using soluble E- or P-selectin competitively binding to their respective ligands indicates that P-selectin engaging PSGL-1 to activate LFA-1 manipulates PMN transmigration at the first 15 minutes, while E-selectin engaging PSGL-1 to activate LFA-1 only influences PMN transmigration after 15 minutes. These results give direct evidences of the distinct and dynamic contributions of P- and E-selectin in mediating neutrophils transmigration, and will provide new mechanistic insights into neutrophils interacting with the vessel wall.