Hydrogen peroxide-induced endothelial retraction is accompanied by a loss of the normal spatial organization of endothelial cell adhesion molecules.
Treatment of confluent monolayers of human umbilical vein endothelial cells with sublethal concentrations of hydrogen peroxide (H2O2) produces reversible cell retraction that opens gaps between adjacent cells. Despite the retraction, adjacent cells remain in contact through a network of dendrite-like processes. Retraction depends on cellular metabolism but not new protein synthesis or protein kinase C. Shape changes induced by H2O2 are accompanied by partial redistribution of actin filaments from the cell periphery in resting endothelial cells to a tangled network of centrally located filaments in H2O2-treated endothelial cells. This change in actin organization is associated with a loss of the normal distribution pattern of surface protein expression. Specifically, beta 1 and beta 3 integrins partly escape from focal adhesion plaques and migrate to the lateral and apical surface of the cell; PECAM-1 redistributes from the lateral borders to the basal surface; and ICAM-1 and ICAM-2 spread from apical caps to the basal surface and to the dendrite-like processes. The likely consequence of endothelial retraction accompanied by abnormal membrane protein distribution is a loss of normal endothelial cell functions. These changes are best considered manifestations of H2O2-induced sublethal injury that may cause endothelial dysfunction.
Bradley
J R
JR
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, United Kingdom.
Thiru
S
S
Pober
J S
JS
D000199:Actins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005110:Extracellular Space; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D014018:Tissue Distribution
D000199:Actins; D015815:Cell Adhesion Molecules; D006861:Hydrogen Peroxide