Soluble CD40L is associated with increased oxidative burst and neutrophil extracellular trap release in Behcet's disease

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Perazzio, Sandro Felix ^{[1, 2, 3, 4]} ; Soeiro-Pereira, Paulo Vitor ^{[5, 6]} ; dos Santos, Viviane Cardoso ^[1] ; de Brito, Marlon Vilela ^[7] ; Salu, Bruno ^[7] ; Vilela Oliva, Maria Luiza ^[7] ; Stevens, Anne Margherite ^{[3, 4]} ; Silva de Souza, Alexandre Wagner ^{[1, 2]} ; Ochs, Hans D. ^{[3, 4]} ; Torgerson, Troy R. ^{[3, 4]} ; Condino-Neto, Antonio ^[5] ; Coelho Andrade, Luis Eduardo ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Div Rheumatol, Rua Botucatu 740, 3 Andar, BR-04023062 Sao Paulo, SP - Brazil

^[2] Fleury Grp Res & Dev, Ave Gen Valdomiro de Lima 508, BR-04344070 Sao Paulo, SP - Brazil

^[3] Univ Washington, Seattle Childrens Res Inst, 1900 9th Ave, JMB 7, Seattle, WA 98101 - USA

^[4] Ctr Immun & Immunotherapies, 1900 9th Ave, JMB 7, Seattle, WA 98101 - USA

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Avenida Prof Lineu Prestes 2415, BR-03178200 Sao Paulo, SP - Brazil

^[6] Univ Fed Maranhao, Dept Pathol, Ave Portugueses, BR-65065545 Sao Luis, MA - Brazil

^[7] Univ Fed Sao Paulo, Dept Biochem & Mol Biol, Escola Paulista Med, Rua Tres de Maio 100, 5 Andar, BR-04044020 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARTHRITIS RESEARCH & THERAPY; v. 19, OCT 19 2017.
• Citações Web of Science: 11

Resumo

Background: Studies have suggested that soluble factors in plasma from patients with active (aBD) and inactive (iBD) Behcet's disease (BD) stimulate neutrophil function. Soluble CD40 ligand (sCD40L) is an important mediator of inflammation in BD. Its expression and effect on neutrophil oxidative burst and neutrophil extracellular trap (NET) release have not been characterized. In this study, we sought to investigate the role of plasma and the CD40L pathway on NET release and the oxidative burst profile in patients with aBD and iBD. Methods: Neutrophils and peripheral blood mononuclear cells (PBMCs) were obtained from patients with aBD (n = 30), patients with iBD (n = 31), and healthy control subjects (HCs; n = 30). sCD40L plasma concentration was determined in individual samples. A pool of plasma for each group was created. In some experiments, plasma pools were treated with recombinant CD40 (rhCD40-muIg) for sCD40L blockade. NET release and H2O2/O-2-production were determined after stimulation with phorbol 12-myristate 13-acetate, sCD40L, or plasma pool. Flow cytometric analysis was performed to evaluate the expression of (1) CD40, Mac-1, and phosphorylated NF-kappa B p65 on neutrophils and monocytes and (2) CD40L on activated T cells and platelets. CD40L gene expression in PBMCs was determined by qRT-PCR. Results: sCD40L plasma levels were significantly higher in patients with iBD (median 17,234, range 2346-19,279 pg/ml) and patients with aBD (median 18,289, range 413-19,883 pg/ml) than in HCs (median 47.5, range 33.7-26.7 pg/ml; p < 0. 001). NET release was constitutively increased in BD compared with HC. NET release and H2O2/O-2-were higher after stimulation with sCD40L or BD plasma and decreased after sCD40L blockade. Mac-1 expression was constitutively increased in neutrophils of patients with aBD (88.7 +/- 13.2% of cells) and patients with iBD (89.2 +/- 20.1% of cells) compared with HC (27.1 +/- 18.8% of cells; p < 0.01). CD40 expression on phagocytes and CD40L expression on platelets were similar in the three groups. PBMCs as well as nonactivated and activated CD4(+) T cells from patients with BD showed higher CD40L expression. Conclusions: Plasma from patients with aBD exerts a stimulus on NET release and oxidative burst, probably induced by sCD40L. (AU)

• Processo FAPESP: 11/50292-2 - Aspectos da imunidade inata na doenca de behcet: um modelo de doenca autoinflamatoria?
• Beneficiário: Luiz Eduardo Coelho Andrade
• Modalidade de apoio: Auxílio à Pesquisa - Regular