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Dynamic contributions of P‐ and E‐selectins to β 2 ‐integrin‐induced neutrophil transmigration
Author(s) -
Gong Yixin,
Zhang Yan,
Feng Shiliang,
Liu Xiaofeng,
Lü Shouqin,
Long Mian
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600398rrr
Subject(s) - selectin , integrin , microbiology and biotechnology , cd18 , umbilical vein , cell adhesion molecule , e selectin , cd44 , immunology , chemistry , endothelium , cell adhesion , biology , in vitro , biochemistry , receptor , cell , endocrinology
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 β 2 ‐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 2 ‐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 2 ‐integrin‐induced neutrophil transmigration. FASEB J. 31, 212–223 (2017) www.fasebj.org