Circulating activated endothelial cells in systemic lupus erythematosus: Further evidence for diffuse vasculopathy

Abstract

OBJECTIVE: In flares of systemic lupus erythematosus (SLE), endothelial cells (EC; activated by immune stimuli) are potential participants in the inflammatory processes that contribute to tissue damage. Accordingly, elevated levels of circulating endothelial cells (CEC) may be a marker for vascular injury. This study was undertaken to examine the possibility that stimulated EC are found in the circulation in patients with active SLE. METHODS: The study cohort included 38 patients with SLE and 16 healthy controls. Immunostaining was performed on mononuclear isolates, using mouse P1H12 (endothelial-specific antibody) and rabbit antinitrotyrosine (a "footprint" of a reactive form of nitric oxide [peroxynitritel). RESULTS: Levels of CEC were significantly higher in patients with active SLE compared with those in healthy controls (mean +/- SEM 32+/-7/ml versus 5+/-2/ml; P = 0.0028) and were correlated positively with plasma C3a in these patients (r = 0.81, P = 0.0008). Furthermore, CEC from these patients expressed an activated phenotype, as indicated by staining for nitrotyrosine. CONCLUSION: Elevated levels of CEC observed in patients with active SLE may represent a marker of endothelial injury. The activated phenotype of these cells suggests that they may be capable of further potentiating vascular injury by the production of inflammatory and prothrombotic mediators and engaging in heterotypic aggregation with neutrophils or platelets.