The Antimicrobial Activity of Peripheral Blood Neutrophils Is Altered in Patients with Primary Ciliary Dyskinesia
Abstract
:1. Introduction
2. Results
2.1. Patients and Controls
2.2. Peripheral Blood Neutrophils from Patients with PCD Show Reduced Chemotactic Response to fMLF in Three Chemotaxis Assays
2.3. Compared to Peripheral Blood Neutrophils of Healthy Individuals, Neutrophils from Patients with PCD Express Similar Adhesion Molecule Levels upon Stimulation
2.4. The Phagocytic Capacity of Peripheral Blood Neutrophils Is Not Affected in Patients with PCD
2.5. Peripheral Blood PMNs from Patients with PCD Produce Less Reactive Oxygen Species Compared to PMNs from Age-Matched Pediatric Controls
2.6. Circulating PMNs from Patients with PCD Tend to Release Less Neutrophil Extracellular Traps Compared to PMNs from Healthy Adults
2.7. Peripheral Blood Neutrophils from Patients with PCD Produce Less CXCL8 Compared to Neutrophils from Healthy Children
3. Discussion
4. Materials and Methods
4.1. Patients and Healthy Controls
4.2. Sample Collection and Processing
4.3. Reagents
4.4. Boyden Chamber Chemotaxis Assay
4.5. Shape Change Assay
4.6. µ-Slide 2D Chemotaxis Assay
4.7. Flow Cytometry
4.8. Adhesion Molecule Activity Assay
4.9. Phagocytosis Assay
4.10. Respiratory Burst Assay
4.11. Neutrophil Extracellular Trap (NET) Assay
4.12. Cell Induction
4.13. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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PCD | Healthy Adult Controls (Ad CO) | Healthy Pediatric Controls (Ped CO) | |
---|---|---|---|
Female/Male No. | 21/27 (44%/56%) | 16/5 (76%/24%) | 23/10 (70%/30%) |
Age, median (range) in years | 14 (3–69) | 27.0 (23–44) | 11.1 (4–18) |
Pediatric/Adult No. | 32/16 (67%/33%) | 0/21 (0%/100%) | 33/0 (100%/0%) |
Ultrastructural defect | |||
Normal ultrastructure | 20/48 (42%) | ||
ODA deficiency | 20/48 (42%) | ||
IDA deficiency + CP abnormalities | 3/48 (6%) | ||
CP deficiency | 4/48 (8%) | ||
Ciliary aplasia | 1/48 (2%) | ||
Genetic abnormalities | |||
Unknown | 8/48 (17%) | ||
DNAH11 | 13/48 (27%) | ||
DNAH5 | 11/48(23%) | ||
DNAAF1 | 3/48 (6%) | ||
SPAG1 | 2/48 (4%) | ||
CCDC39 | 1/48 (2%) | ||
CCDC40 | 2/48 (4%) | ||
CCDC65 | 1/48 (2%) | ||
CCDC103 | 2/48 (4%) | ||
HYDIN | 1/48 (2%) | ||
RSPH1 | 1/48 (2%) | ||
RSPH4 | 1/48 (2%) | ||
RSPH9 | 1/48 (2%) | ||
OFD1 | 1/48 (2%) | ||
Clinical features | |||
Bronchiectasis | 33/48 (69%) | ||
Situs inversus | 17/48 (35%) | ||
FEV1, median (range) (%) | 92 (43–113) | ||
FVC, median (range) (%) | 100 (76–125) | ||
Laboratory features, median (range) | |||
WBC count (/µL) | 7415 (3900–17,240) | ||
CRP (mg/dL) | 1.1 (<0.3–10.2) | ||
Sputum bacteria | |||
H. influenzae | 10/48 (21%) | ||
P. aeruginosa | 7/48 (15%) | ||
S. aureus | 10/48 (21%) | ||
S. pneumoniae | 4/48 (8%) | ||
Treatment | |||
Azithromycin | 6/48 (13%) | ||
Oral antibiotics | 3/48 (6%) | ||
Inhaled antibiotics | 2/48 (4%) | ||
Inhaled steroids | 1/48 (2%) |
Neutrophil Function | CF | COPD | Asthma | PCD |
---|---|---|---|---|
Phagocytosis | =[46] | =/↓[48] | ↑[25,49] | = |
ROS production | ≠[27,50] | ↑[43] | =/↑[25,45,51] | ↓ |
NET formation | ↑[24,47] | NA | NA | ↓ |
CXCL8 production | ↑[52,53] | NA | =/↑[29,54] | ↓ |
Chemotaxis | ≠[55,56,57] | ↑[28] | ↑[49] | ↓ |
Adhesion molecules | =[41,42] | ↑[43,44] | ↑[49] | = |
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Cockx, M.; Blanter, M.; Gouwy, M.; Ruytinx, P.; Abouelasrar Salama, S.; Knoops, S.; Pörtner, N.; Vanbrabant, L.; Lorent, N.; Boon, M.; et al. The Antimicrobial Activity of Peripheral Blood Neutrophils Is Altered in Patients with Primary Ciliary Dyskinesia. Int. J. Mol. Sci. 2021, 22, 6172. https://doi.org/10.3390/ijms22126172
Cockx M, Blanter M, Gouwy M, Ruytinx P, Abouelasrar Salama S, Knoops S, Pörtner N, Vanbrabant L, Lorent N, Boon M, et al. The Antimicrobial Activity of Peripheral Blood Neutrophils Is Altered in Patients with Primary Ciliary Dyskinesia. International Journal of Molecular Sciences. 2021; 22(12):6172. https://doi.org/10.3390/ijms22126172
Chicago/Turabian StyleCockx, Maaike, Marfa Blanter, Mieke Gouwy, Pieter Ruytinx, Sara Abouelasrar Salama, Sofie Knoops, Noëmie Pörtner, Lotte Vanbrabant, Natalie Lorent, Mieke Boon, and et al. 2021. "The Antimicrobial Activity of Peripheral Blood Neutrophils Is Altered in Patients with Primary Ciliary Dyskinesia" International Journal of Molecular Sciences 22, no. 12: 6172. https://doi.org/10.3390/ijms22126172