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...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6144 |
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| author | Antonio Muñoz-Callejas Elena González-Sánchez Javier Silván Esther San Antonio Rafael González-Tajuelo Alejandra Ramos-Manzano Inés Sánchez-Abad Isidoro González-Alvaro Javier García-Pérez Eva G. Tomero Rosario García de Vicuña Esther F. Vicente-Rabaneda Santos Castañeda Ana Urzainqui |
| author_facet | Antonio Muñoz-Callejas Elena González-Sánchez Javier Silván Esther San Antonio Rafael González-Tajuelo Alejandra Ramos-Manzano Inés Sánchez-Abad Isidoro González-Alvaro Javier García-Pérez Eva G. Tomero Rosario García de Vicuña Esther F. Vicente-Rabaneda Santos Castañeda Ana Urzainqui |
| author_sort | Antonio Muñoz-Callejas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:36:02Z |
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| id | doaj.art-a12b7fb1f2ba45f3baf8063acf11a674 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:02Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a12b7fb1f2ba45f3baf8063acf11a6742023-11-17T16:47:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247614410.3390/ijms24076144Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus ErythematosusAntonio Muñoz-Callejas0Elena González-Sánchez1Javier Silván2Esther San Antonio3Rafael González-Tajuelo4Alejandra Ramos-Manzano5Inés Sánchez-Abad6Isidoro González-Alvaro7Javier García-Pérez8Eva G. Tomero9Rosario García de Vicuña10Esther F. Vicente-Rabaneda11Santos Castañeda12Ana Urzainqui13Immunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainRheumatology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainPulmonology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainRheumatology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainRheumatology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainRheumatology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainImmunology Department, Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, 28006 Madrid, SpainSystemic 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.https://www.mdpi.com/1422-0067/24/7/6144PSGL-1P-selectinneutrophilsSLE pathogenesisNETs |
| spellingShingle | Antonio Muñoz-Callejas Elena González-Sánchez Javier Silván Esther San Antonio Rafael González-Tajuelo Alejandra Ramos-Manzano Inés Sánchez-Abad Isidoro González-Alvaro Javier García-Pérez Eva G. Tomero Rosario García de Vicuña Esther F. Vicente-Rabaneda Santos Castañeda Ana Urzainqui Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus International Journal of Molecular Sciences PSGL-1 P-selectin neutrophils SLE pathogenesis NETs |
| title | Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus |
| title_full | Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus |
| title_fullStr | Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus |
| title_full_unstemmed | Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus |
| title_short | Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus |
| title_sort | low p selectin glycoprotein ligand 1 expression in neutrophils associates with disease activity and deregulated net formation in systemic lupus erythematosus |
| topic | PSGL-1 P-selectin neutrophils SLE pathogenesis NETs |
| url | https://www.mdpi.com/1422-0067/24/7/6144 |
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