Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus
Abstract
:1. Introduction
2. Results
2.1. PSGL-1 Expression Is Reduced in Neutrophils of Active SLE Patients
2.2. PSGL-1 Is Located in the NETs
2.3. Neutrophils from SLE Patients Are More Susceptible to Generate NETs
2.4. PSGL-1/P-Selectin Interaction Modulates NET Generation in HD
2.5. PSGL-1/P-Selectin Interaction Does Not Control DNA Extrusion in SLE Patients with Active Disease
2.6. PSGL-1/P-Selectin Interaction Signaling Is Altered in SLE Patients
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Labeling of Neutrophils for Flow Cytometry
4.3. Neutrophils Isolation
4.4. Rolling-like Assays
4.5. Activation with PMA
4.6. Quantification of NETs by Fluorometry, Confocal Microscopy and Flow Cytometry
4.7. Phospho-Syk Measurement by Flow Cytometry
4.8. Confocal Image Analysis of NETs
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SLE Patients | Inactive SLE (n = 33) | Active SLE (n = 14) | p-Value |
---|---|---|---|
Female/Male, n (%) | 30 (90)/3 (10) | 13 (92)/1 (8) | |
Age (years), mean [min–max] | 50.35 [23–83] | 43.28 [19–59] | |
Disease duration (years), mean [min–max] | 13.79 [1 month–38 years] | 8.57 [1 month–21 years] | |
ANA + profile, n (%) | 32 (96) | 14 (100) | |
Anti-ds-DNA + profile, n (%) | 13 (39) | 13 (92) *** | 0.0010 |
Anti-Sm + profile, n (%) | 5 (15) | 3 (21) | 0.6795 |
Lupus anticoagulant | 5 (15) | 5 (35) | 0.1373 |
SLICC/ACR Damage Index (mean [min–max]) | 0.57 [0–4] | 0.71 [0–3] | 0.1436 |
SLEDAI (mean [min–max]) | 1.11 [0–4] | 14.14 [6–41] **** | <0.0001 |
Renal manifestations, n (%) | 15 (45) | 12 (85) * | 0.0220 |
Lung manifestations, n (%) | 5 (15) | 5 (35) | 0.1171 |
Raynaud´s phenomenon | 6 (18) | 3 (21) | 0.5435 |
Treatment, n (%) | |||
Azathioprine | 15 (45) | 8 (57) | |
Belimumab | 2 (6) | 4 (28) | |
Glucocorticoids | 29 (87) | 13 (92) | |
Hydroxychloroquine | 30 (90) | 14 (100) | |
Methotrexate | 9 (27) | 4 (28) | |
Mycophenolate mofetil | 4 (11) | 12 (85) | |
Rituximab | 6 (18) | 5 (35) |
SLE Patients | Inactive SLE (n = 7) | Active SLE (n = 8) | p-Value |
---|---|---|---|
Female/Male, n (%) | 7 (100) | 7 (87)/1 (13) | |
Age (years), mean [min–max] | 48.85 [24–63] | 29.87 [23–54] | |
Disease duration (years), mean [min–max] | 25 [5–38 years] | 5.08 [1 month–16 years] | |
ANA + profile, n (%) | 6 (85) | 8 (100) | |
Anti-ds-DNA + profile, n (%) | 2 (28) | 8 (100) *** | 0.0070 |
Anti-Sm + profile, n (%) | 1 (14) | 5 (62) | 0.1189 |
Lupus anticoagulant | 1 (14) | 2 (25) | 0.5515 |
SLICC/ACR Damage Index (mean [min–max]) | 0.57 [0–3] | 1 [0–3] | 0.1883 |
SLEDAI (mean [min–max]) | 2.85 (0–4) | 14 (11–23) *** | 0.0013 |
Renal manifestations, n (%) | 4 (57) | 7 (87) | 0.2821 |
Lung manifestations, n (%) | 1 (14) | 3 (37) | 0.3392 |
Raynaud´s phenomenon | 1 (14) | 2 (25) | 0.5545 |
Treatment, n (%) | |||
Azathioprine | 0 (0) | 1 (12) | |
Glucocorticoids | 3 (42) | 7 (87) | |
Cyclophosphamide | 0 (0) | 1 (12) | |
Hydroxychloroquine | 2 (28) | 6 (75) | |
Methotrexate | 1 (14) | 2 (25) | |
Mycophenolate mofetil | 3 (42) | 1 (12) |
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Muñoz-Callejas, A.; González-Sánchez, E.; Silván, J.; San Antonio, E.; González-Tajuelo, R.; Ramos-Manzano, A.; Sánchez-Abad, I.; González-Alvaro, I.; García-Pérez, J.; Tomero, E.G.; et al. Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus. Int. J. Mol. Sci. 2023, 24, 6144. https://doi.org/10.3390/ijms24076144
Muñoz-Callejas A, González-Sánchez E, Silván J, San Antonio E, González-Tajuelo R, Ramos-Manzano A, Sánchez-Abad I, González-Alvaro I, García-Pérez J, Tomero EG, et al. 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. 2023; 24(7):6144. https://doi.org/10.3390/ijms24076144
Chicago/Turabian StyleMuñoz-Callejas, Antonio, 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, and et al. 2023. "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 24, no. 7: 6144. https://doi.org/10.3390/ijms24076144