Live-cell visualization of the trans-cellular mode of monocyte transmigration across the vascular endothelium, and its relationship with endothelial PECAM-1
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In response to atherogenic stimuli, blood monocytes transmigrate across the vascular endothelium not only through endothelial cell–cell junctions (para-cellular) but also through endothelial cells themselves (trans-cellular). The molecular mechanism of the latter is mostly unknown, because it rarely happens, especially in vitro. Although many reports have recognized trans-cellular migration from snapshot images of leukocytes halfway across the endothelium at non-junctional locations, it often produces a false-positive result, because some leukocytes that initiate trans-cellular migration withdraw and return to the apical endothelial surface. Thus, analyzing the entire process is essential. In this study, complete monocyte trans-cellular migration was successfully captured for live cells, with simultaneous visualization of endothelial PECAM-1. We suggest the possible existence of both PECAM-1-related migration at peri-junctional sites and PECAM-1-unrelated migration at sites remote from junctions. This is the first report to describe the entire process of monocyte trans-cellular migration for live cells and its relationship with endothelial PECAM-1.
KeywordsAtherosclerosis Leukocyte Endothelium Trans-cellular migration PECAM-1
This work was supported in part by Grant-in-Aid for Scientific Research in Japan (18300156 and 19700391), and grants from Kawasaki Medical School (Project-Research 18-306T and 19-314Y). Ken Hashimoto is also supported by grants from Takeda Science Foundation (Japan) for research on monocyte trans-endothelial migration.
Conflict of interest
The authors declare that they have no conflict of interest.
Supplementary material 1 (AVI 986 kb)
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