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 LPS-treated 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.
Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Beijing Key Laboratory Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; and.
Yixin
Y
Gong
Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Beijing Key Laboratory Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; and.|School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
Yan
Y
Zhang
Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Beijing Key Laboratory Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; and.
Shiliang
S
Feng
Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Beijing Key Laboratory Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; and.
Xiaofeng
X
Liu
Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Beijing Key Laboratory Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; and.|School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
Shouqin
S
Lü
Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; mlong@imech.ac.cn.|Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.|Beijing Key Laboratory Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; and.|School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
Mian
M
Long
D002460:Cell Line; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology
D019040:E-Selectin; D039641:Integrin beta Chains; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D018799:Intercellular Adhesion Molecule-1; D005346:Fibroblast Growth Factors
CD44; PSGL-1; synergic mechanisms