Diesel exhaust particle exposure causes redistribution of endothelial tube VE-cadherin.
Whether diesel exhaust particles (DEPs) potentially have a direct effect on capillary endothelia was examined by following the adherens junction component, vascular endothelial cell cadherin (VE-cadherin). This molecule is incorporated into endothelial adherens junctions at the cell surface, where it forms homodimeric associations with adjacent cells and contributes to the barrier function of the vasculature (Dejana et al., 2008; Venkiteswaran et al., 2002; Villasante et al., 2007). Human umbilical vein endothelial cells (HUVECs) that were pre-formed into capillary-like tube networks in vitro were exposed to DEPs for 24h. After exposure, the integrity of VE-cadherin in adherens junctions was assessed by immunofluorescence analysis, and demonstrated that increasing concentrations of DEPs caused increasing redistribution of VE-cadherin away from the cell-cell junctions toward intracellular locations. Since HUVEC tube networks are three-dimensional structures, whether particles entered the endothelial cells or tubular lumens was also examined. The data indicate that translocation of the particles does occur. The results, obtained in a setting that removes the confounding effects of inflammatory cells or blood components, suggest that if DEPs encounter alveolar capillaries in vivo, they may be able to directly affect the endothelial cell-cell junctions.
Chao
Ming-Wei
MW
Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854, USA.
Kozlosky
John
J
Po
Iris P
IP
Strickland
Pamela Ohman
PO
Svoboda
Kathy K H
KK
Cooper
Keith
K
Laumbach
Robert J
RJ
Gordon
Marion K
MK
D022005:Adherens Junctions / Q000378:metabolism; D015703:Antigens, CD / Q000187:drug effects* / Q000378:metabolism; D015820:Cadherins / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D052638:Particulate Matter / Q000633:toxicity*; D014471:Umbilical Veins; D001335:Vehicle Emissions / Q000633:toxicity*; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D052638:Particulate Matter; D001335:Vehicle Emissions; D000099152:Cadherin 5