title: Platelet-mediated adhesion facilitates leukocyte sequestration in hypoxia-reoxygenated microvessels.
abstract: Leukocyte transendothelial migration and sequestration are two distinct outcomes following leukocyte adhesion to endothelium during ischemia-reperfusion injury, in which platelets may play a pivotal role. In the present study, we established an in vitro hypoxia-reoxygenation model to mimic ischemia-reperfusion injury and found platelet pre-incubation significantly increased leukocyte adhesion to endothelial cells after hyoxia-reoxygenation (over 67%). Blockade of endothelial-cell-expressed adhesion molecules inhibited leukocyte direct adhesion to endothelial cells, while platelet-mediated leukocyte adhesion was suppressed by blockade of platelet-expressed adhesion molecules. Further experiments revealed platelets acted as a bridge to mediate leukocyte adhesion, and platelet-mediated adhesion was the predominant pattern in the presence of platelets. However, platelet pre-incubation significantly suppressed leukocyte transendothelial migration after hypoxia-reoxygenation (over 31%), which could be aggravated by blockade of endothelial-cell-expressed adhesion molecules, but alleviated by blockade of platelet- expressed adhesion molecules. This would indicate that platelet-mediated adhesion disrupted leukocyte transendothelial migration. An in vivo mesenteric ischemia-reperfusion model demonstrated leukocyte transfusion alone caused mild leukocyte adhesion to reperfused vessels and subsequent leukocyte infiltration, while simultaneous leukocyte and platelet transfusion led to massive leukocyte adhesion and sequestration within reperfused microvessels. Our studies revealed platelets enhanced leukocyte adhesion to endothelial cells, but suppressed leukocyte transendothelial migration. Overall, this leads to leukocyte sequestration in hypoxia-reoxygenated microvessels.
authors.affiliation: Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Senfeng
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.affiliation: Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, 100029, China. chenghui_li@sina.com.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Li
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D055806:Microvessels / Q000166:cytology / Q000503:physiopathology*; D008954:Models, Biological; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D015815:Cell Adhesion Molecules
keywords: adhesion; endothelial cells; hypoxia-reoxygenation; leukocytes; platelets; transendothelial migration