Abstract
BackgroundCirculating endothelial progenitor cells (EPCs) are biologic markers of endothelial function. In patients with systemic lupus erythematosus (SLE), the numerical reduction and functional impairment of EPCs contribute to the endothelial dysfunction.Through ex vivo and in vitro studies, we aimed at evaluating the effects of B lymphocyte stimulator (BLyS) on EPC colonies and endothelial cells and also investigating BLyS receptor expression on these cells.MethodsEPCs were isolated from peripheral blood mononuclear cells (PBMC). In order to evaluate their ability to form colonies, EPCs were cultured on fibronectin-coated dishes and incubated with BlyS alone or BlyS and belimumab. Apoptosis of EPCs and endothelial cell line EA.hy926 was evaluated after 6, 12, and 24 h of incubation with BLyS and after 6 h with BLyS and belimumab. The expression of B cell activating factor-receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) on EPCs and EA.hy926 was analyzed by cytofluorimetry.ResultsThe number of EPC colonies was lower in patients than in controls. Moreover, the colonies from SLE patients were poorly organized compared to controls; the addition of belimumab restored the colony structure. Incubation with BLyS induced apoptosis of EPCs and EA.hy926 that was inhibited by the co-incubation with belimumab. BAFF-R and BCMA were expressed on both EPCs and EA.hy926, while TACI was expressed only on EPCs.ConclusionsEPCs and endothelial cells preferentially express BAFF-R which could be involved in the pro-apoptotic effect of BlyS. Belimumab administration seems to restore the quantitative and qualitative changes of EPC colonies both ex vivo and in vitro.
Highlights
Circulating endothelial progenitor cells (EPCs) are biologic markers of endothelial function
Recent experimental evidence could suggest a role of B lymphocyte stimulator (BLyS) in atherosclerosis: B cell activating factor (BAFF)-R-deficient mice, as well as in mice treated with an anti-BAFF monoclonal antibody, experienced a reduction of the atherosclerotic plaque size [14]
Apoptosis of endothelial progenitor cells and EA.hy926 endothelial cells (EC) We investigated the apoptotic potential of BLyS by treating EPCs with different BLyS concentrations (Fig. 5a)
Summary
Circulating endothelial progenitor cells (EPCs) are biologic markers of endothelial function. In patients with systemic lupus erythematosus (SLE), the numerical reduction and functional impairment of EPCs contribute to the endothelial dysfunction. Through ex vivo and in vitro studies, we aimed at evaluating the effects of B lymphocyte stimulator (BLyS) on EPC colonies and endothelial cells and investigating BLyS receptor expression on these cells. Circulating endothelial progenitor cells (EPCs) are bone marrow-derived precursors which differentiate into mature endothelial cells and contribute to new vessel formation and vascular homeostasis [1]. Several studies suggested that numerical and functional impairment of EPCs detected in SLE patients contribute to the endothelial dysfunction [7,8,9,10,11]. Data in humans are still lacking and, to the best of our knowledge, no previous studies investigated the effect of BLyS on endothelial progenitor cells and mature endothelial cells
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