Background: 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 also investigating BLyS receptor expression on these cells. Methods: EPCs 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. Results: The 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. Conclusions: EPCs 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.

B lymphocyte stimulator modulates number and function of endothelial progenitor cells in systemic lupus erythematosus / Spinelli, F. R.; Barbati, C.; Cecarelli, F.; Morello, F.; Colasanti, T.; Vomero, M.; Massaro, L.; Orefice, V.; Alessandri, C.; Valesini, G.; Conti, F.. - In: ARTHRITIS RESEARCH & THERAPY. - ISSN 1478-6354. - 21:1(2019), p. 245. [10.1186/s13075-019-2015-7]

B lymphocyte stimulator modulates number and function of endothelial progenitor cells in systemic lupus erythematosus

Spinelli F. R.;Barbati C.;Morello F.;Colasanti T.;Vomero M.;Massaro L.;Orefice V.;Alessandri C.;Valesini G.;Conti F.
2019

Abstract

Background: 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 also investigating BLyS receptor expression on these cells. Methods: EPCs 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. Results: The 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. Conclusions: EPCs 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.
2019
Atherosclerosis; Belimumab; BLyS; Endothelial progenitor cells; Systemic lupus erythematosus; Adult; Antibodies, Monoclonal, Humanized; Apoptosis; B-Cell Activating Factor; B-Cell Activation Factor Receptor; B-Cell Maturation Antigen; Cell Count; Cell Line; Cells, Cultured; Endothelial Progenitor Cells; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Middle Aged; Stem Cells; Transmembrane Activator and CAML Interactor Protein
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B lymphocyte stimulator modulates number and function of endothelial progenitor cells in systemic lupus erythematosus / Spinelli, F. R.; Barbati, C.; Cecarelli, F.; Morello, F.; Colasanti, T.; Vomero, M.; Massaro, L.; Orefice, V.; Alessandri, C.; Valesini, G.; Conti, F.. - In: ARTHRITIS RESEARCH & THERAPY. - ISSN 1478-6354. - 21:1(2019), p. 245. [10.1186/s13075-019-2015-7]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1495216
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