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Oxidized LDL specifically promotes the initiation of monocyte invasion at cell‐cell junctions by upregulating PECAM‐1
Author(s) -
Hashimoto Ken,
Kataoka Noriyuki,
Nakamura Emi,
Tsujioka Katsuhiko,
Kajiya Fumihiko
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a862-b
Subject(s) - monocyte , microbiology and biotechnology , umbilical vein , chemistry , downregulation and upregulation , cell adhesion , endothelium , adhesion , cell adhesion molecule , cell , human umbilical vein endothelial cell , in vitro , immunology , biology , biochemistry , endocrinology , organic chemistry , gene
Oxidized LDL (oxLDL) has been reported to activate vascular endothelial cells and promote monocyte diapedesis. But how and on which steps oxLDL affects the monocyte dynamics has been poorly addressed. Using human umbilical vein endothelial cells and freshly‐isolated human monocytes, we developed an in vitro proatherogenic model with oxLDL embedded in very thin (30–50 μm) subendothelial collagen gels. This model resembled the subendothelial accumulation of oxLDL in atherosclerotic plaques in vivo , and enabled to track 3D‐kinetics of individual living monocytes by confocal laser scanning microscopy. We divided the monocyte dynamics into three steps (1. adhesion, 2. diapedesis at cell‐cell junctions, 3. migration under endothelium), and found that oxLDL specifically and significantly increased the number of adherent monocytes that started diapedesis at junctions (step 1–2), but had no effect thereafter (step 2–3). Migration speed of each monocyte was not affected by oxLDL throughout the whole process (step 1–3). To explore the role of oxLDL, we examined the expression of platelet endothelial cell adhesion molecule‐1 (PECAM‐1) by western blotting, and showed that both hydrophobic (membrane‐bound) and hydrophilic (cytosolic) PECAM‐1 significantly increased in the presence of oxLDL. Upregulation of PECAM‐1 by oxLDL may promote monocyte priming at junctions to start diapedesis. Source of research support: The Ministry of Education, Culture, Sports, Science and Technology of Japan (K.H. and K.T.).