Monocyte trans-endothelial migration augments subsequent transmigratory activity with increased PECAM-1 and decreased VE-cadherin at endothelial junctions

• Published in: International journal of cardiology 2011-06, Vol.149 (2), p.232-239
• Main Authors: Hashimoto, Ken, Kataoka, Noriyuki, Nakamura, Emi, Hagihara, Kimiko, Hatano, Mizue, Okamoto, Takeaki, Kanouchi, Hiroaki, Minatogawa, Yohsuke, Mohri, Satoshi, Tsujioka, Katsuhiko, Kajiya, Fumihiko
• Format: Article
• Language: English
• Subjects: Antigens, CD - biosynthesis; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cadherins - antagonists & inhibitors; Cadherins - biosynthesis; Cardiology. Vascular system; Cardiovascular; Cells, Cultured; Down-Regulation - physiology; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Humans; Intercellular Junctions - metabolism; Intercellular Junctions - physiology; Medical sciences; Monocyte; Monocytes - cytology; Monocytes - physiology; PECAM-1; Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis; Platelet Endothelial Cell Adhesion Molecule-1 - physiology; Transendothelial and Transepithelial Migration - physiology; Transmigration; Up-Regulation - physiology; VE-cadherin
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2010.12.018

Abstract Background Although the importance of monocyte trans-endothelial migration in early atherogenesis is well recognized, it is unclear whether and how one transmigration event affects endothelium to facilitate subsequent ones. In this study, we tested the hypothesis that monocyte transmigration alters endothelial junctional organization to facilitate subsequent transmigration. Methods and results When human monocytes were added twice at intervals of ≈ 30 min to IL-1beta-prestimulated human umbilical vein endothelial cells in vitro , significant augmentation of transmigration was observed at the second addition (≈ 1.5-fold, analyzed from a total of 231 monocytes in 3 experiments). Endothelial surface expressions of two major junctional molecules, PECAM-1 and VE-cadherin, increased and decreased respectively, in response to monocyte addition, which could facilitate subsequent transmigration. To further investigate spatiotemporal dynamics of the increasing molecule, PECAM-1, we constructed a PECAM-1-GFP expression system and found that monocyte transmigration induced local accumulation of endothelial PECAM-1 around the transmigration spot, which was followed by transmigration of subsequent monocyte around the same location. Detailed analysis revealed that within the defined region around one transmigration event, 50% of later transmigrating monocytes used the same or similar location as the previous one (10 out of 20 transmigrating monocytes in 11 experiments). Conclusions These findings show that monocyte trans-endothelial migration alters endothelial junctional organization to a more monocyte-permeable state (increased PECAM-1 and decreased VE-cadherin), resulting in the augmented transmigratory activity at a later stage. This positive feedback mechanism is partially associated with monocyte transmigration-induced local accumulation of endothelial PECAM-1, which promotes transmigration of following monocytes at the same location.