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. adhesion, endothelial cells, hypoxia-reoxygenation, leukocytes, platelets, transendothelial migration Citation:Zheng, S., Cao, Y., Zhang, W., Liu, H., You, J., Yin, Y., Liu, J., and Li, C. (2016). Platelet-mediated adhesion facilitates leukocyte sequestration in hypoxia-reoxygenated microvessels . Sci China Life Sci 59, 299 -311.

Role of Platelet Activation and Oxidative Stress in the Evolution of Myocardial Infarction

“…155 (iii) Platelet-leukocyte interaction: In an in vitro model of ischemia and reperfusion, platelets mediate leukocyte infiltration in reperfused vessels, acting as a bridge between leukocytes and endothelium. 156,157 The mechanisms by which platelet thrombus control leukocytes migration to vascular injury sites involves a gradient of platelet-derived chemokine CXCL7 (also known as NAP-2), a chemokine that binds to CXC chemokine receptor I/2 (CXCRI/2) at leukocytes promoting cells' intravascular migration through platelet thrombi. 158 is a mediator derived from phospholipids that increases differentially in the early reperfusion phase compared to the ischemic and preischemic stages.…”

Modeling changes in vascular and extracellular matrix integrity that can occur in decellularized kidneys after implantation

“…Compared to erythrocytes, leukocyte, and platelet activities, which rely on mitochondrial machinery to meet normal energetic demands, would have also been impacted by this deficiency in nutrients. Mitochondria dysfunction that would have resulted from hypoxia is known to diminish platelet survival severely and again increase the likelihood of vascular thrombosis [26], and leukocyte sequestration [27]. It has also been established that the decellularization process can reduce the mechanical strength of the ECM [28], and diminish the critical support needed to maintain the vasculature.…”