title: Monocyte trans-endothelial migration augments subsequent transmigratory activity with increased PECAM-1 and decreased VE-cadherin at endothelial junctions.
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.
  
  
  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.
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan. Electronic address: khashimo@med.kawasaki-m.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Medical Engineering, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kataoka
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Nakamura
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Hagihara
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Mizue
authors.initials: M
authors.lastname: Hatano
authors.affiliation: Department of Natural Sciences, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Veterinary Pathobiology, Faculty of Agriculture, Kagoshima University, Kagoshima, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kanouchi
authors.affiliation: Department of Biochemistry, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Minatogawa
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mohri
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tsujioka
authors.affiliation: Department of Medical Engineering, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kajiya
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000502:physiology; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5