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

• Published in: The FASEB journal Vol. 31; no. 1; p. 212
• Main Authors: Gong, Yixin, Zhang, Yan, Feng, Shiliang, Liu, Xiaofeng, Lü, Shouqin, Long, Mian
• Format: Journal Article
• Language: English
• Published: United States 01.01.2017
• Subjects: Cell Line; E-Selectin - genetics; E-Selectin - metabolism; Endothelial Cells - metabolism; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Gene Expression Regulation - physiology; Humans; Integrin beta Chains - genetics; Integrin beta Chains - metabolism; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Lipopolysaccharides; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Neutrophils - physiology; P-Selectin - genetics; P-Selectin - metabolism; Protein Binding; Signal Transduction - physiology; synergic mechanisms; PSGL-1; CD44
• ISSN: 1530-6860
• DOI: 10.1096/fj.201600398rrr

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 LPS-treated HUVECs. Blocking and competitive tests indicated that P-selectin engages PSGL-1 to activate β -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 β -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 β -integrin-induced neutrophil transmigration.