Platelet-mediated adhesion facilitates leukocyte sequestration in hypoxia-reoxygenated microvessels
Blood Platelets
0301 basic medicine
Agricultural and Biological Sciences(all)
Biochemistry, Genetics and Molecular Biology(all)
Endothelial Cells
Models, Biological
Cell Hypoxia
Cell Line
3. Good health
03 medical and health sciences
Environmental Science(all)
Cell Movement
Reperfusion Injury
Microvessels
Cell Adhesion
Leukocytes
Humans
Cell Adhesion Molecules
Cells, Cultured
DOI:
10.1007/s11427-015-4986-1
Publication Date:
2016-01-18T15:01:59Z
AUTHORS (8)
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.
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CITATIONS (4)
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