Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus

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 lu...

Descripción completa

Detalles Bibliográficos
Autores: Muñoz Callejas, Antonio|||/items/55dd2545-0281-43d6-974b-4ea33f592740, González-Sánchez, Elena, Silván, Javier, San Antonio, Esther, González-Tajuelo, Rafael, Ramos-Manzano, Alejandra, Sánchez-Abad, Inés, González-Alvaro, Isidoro, García-Pérez, Javier, G. Tomero, Eva, García de Vicuña, Rosario, Vicente-Rabaneda, Esther F., Castañeda, Santos, Urzainqui, Ana
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Alfonso X el Sabio
Repositorio:Repositorio Institucional de la Universidad Alfonso X el Sabio
Idioma:inglés
OAI Identifier:oai:archive.uax.com:20.500.12080/52088
Acceso en línea:https://hdl.handle.net/20.500.12080/52088
Access Level:acceso abierto
Palabra clave:PSGL-1
P-selectina
neutrófilos
SLE pathogenesis
NETs
Descripción
Sumario: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 nticoagulant. 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.