Endothelial cell apoptosis in systemic sclerosis is induced by antibody‐dependent cell‐mediated cytotoxicity via CD95

Objective Apoptosis of endothelial cells is a key event in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to analyze in vitro the mechanism causing endothelial cell apoptosis in SSc. Methods Human dermal microvascular endothelial cells (HDMEC) or human umbilical vein...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Arthritis and rheumatism 2000-11, Vol.43 (11), p.2550-2562
Hauptverfasser: Sgonc, Roswitha, Gruschwitz, Matthias S., Boeck, Guenther, Sepp, Norbert, Gruber, Johann, Wick, Georg
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Objective Apoptosis of endothelial cells is a key event in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to analyze in vitro the mechanism causing endothelial cell apoptosis in SSc. Methods Human dermal microvascular endothelial cells (HDMEC) or human umbilical vein endothelial cells (HUVEC) were cultured with native or heat‐inactivated serum from SSc patients or controls with or without interleukin‐2–activated natural killer (NK) cells or peripheral blood mononuclear cells. SSc and control sera were tested for the presence or absence, respectively, of anti–endothelial cell antibodies (AECA) by indirect immunofluorescence. Apoptosis was detected by the TUNEL technique. Results Native sera alone had no effect. Apoptosis induction was observed on HDMEC, but not on HUVEC, in the presence of AECA‐positive SSc sera and activated NK cells, and could be inhibited by an anti–Fas ligand antibody. Inhibition of the perforin/granzyme pathway with concanamycin A had no effect on apoptosis induction in this in vitro model. Immunofluorescence analysis of cryosections from SSc skin showed Fas (CD95) expression by endothelial cells, supporting the in vitro findings. Conclusion The results suggest that endothelial cell apoptosis in SSc is induced by antibody‐dependent cell‐mediated cytotoxicity via the Fas pathway. These data not only provide insight into the pathogenesis of SSc, but also may open new ways to rational therapy for this disease.
ISSN:0004-3591
1529-0131
DOI:10.1002/1529-0131(200011)43:11<2550::AID-ANR24>3.0.CO;2-H