학술논문
Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus.
Document Type
Article
Author
Muñoz-Callejas, Antonio; González-Sánchez, Elena; Silván, Javier; San Antonio, Esther; González-Tajuelo, Rafael; Ramos-Manzano, Alejandra; Sánchez-Abad, Inés; González-Alvaro, Isidoro; García-Pérez, Javier; Tomero, Eva G.; de Vicuña, Rosario García; Vicente-Rabaneda, Esther F.; Castañeda, Santos; Urzainqui, Ana
Source
Subject
*P-selectin glycoprotein ligand-1
*SYSTEMIC lupus erythematosus
*NEUTROPHILS
*RAYNAUD'S disease
*AUTOIMMUNE diseases
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Language
ISSN
1661-6596
Abstract
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a lupus-like syndrome and patients with cutaneous lupus have reduced P-selectin expression in skin vessels. Using flow cytometry we analyzed in healthy donors and patients the expression of P-selectin Glycoprotein Ligand-1 (PSGL-1) in circulating neutrophils and the implication of PSGL-1/P-selectin interaction in neutrophil extracellular traps (NETs) generation. We found a statistical significance that neutrophils from active SLE patients have a reduced expression of PSGL-1 and low levels of PSGL-1 in neutrophils from SLE patients associated with the presence of anti-dsDNA antibodies, clinical lung involvement, Raynaud's phenomenon, and positive lupus anticoagulant. PSGL-1 is present along the DNA in the NET. In healthy donors, neutrophil interaction with immobilized P-selectin triggers Syk activation, increases the NETs percentage and reduces the amount of DNA extruded in the NETs. In active SLE patients, neutrophil interaction with P-selectin does not activate Syk or reduce the amount of DNA extruded in the NETs, that might contribute to increase the extracellular level of DNA and hence, to disease pathogenesis. [ABSTRACT FROM AUTHOR]