title: Release of soluble E-selectin from activated endothelial cells upon apoptosis.
abstract: Circulating soluble E-selectin is increased in diseases associated with endothelial apoptosis such as sepsis and acute respiratory distress syndrome. We investigated the mechanism by which endothelial cell (EC) apoptosis may promote soluble E-selectin release. We found that serum deprivation of EC caused apoptosis, yet it did not induce E-selectin EC surface expression. Tumor necrosis factor-alpha (TNFalpha) significantly increased EC E-selectin surface expression. Soluble E-selectin was noted, however, only in the medium of TNFalpha-activated, apoptotic EC. Preincubation of the EC with the caspase inhibitor z-VAD-fmk significantly attenuated soluble E-selectin levels in the culture medium of TNFalpha-activated, apoptotic EC, but it had no effect on E-selectin surface expression. These results indicate that TNFalpha activation, but not apoptosis, is necessary for E-selectin surface expression in EC. Furthermore, E-selectin release from EC requires caspase-3 activation. Thus, increased concentrations of circulating E-selectin in serum may serve as a marker for endothelial apoptosis in certain disease states.
authors.affiliation: Vascular Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island 02908, USA. Elizabeth_Harrington@brown.edu
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Harrington
authors.forename: Tihomir
authors.initials: T
authors.lastname: Stefanec
authors.forename: Julie
authors.initials: J
authors.lastname: Newton
authors.forename: Sharon
authors.initials: S
authors.lastname: Rounds
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008856:Microscopy, Fluorescence; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3