Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses
Abstract
:1. Introduction
2. Methods
2.1. Study Design
2.2. Animals
2.3. Measurement of Tissue and Serum Monoamines and Their Metabolites Via HPLC
2.4. LPS Administration
2.5. Blood Collection and PBMC Isolation
2.6. Peritoneal Macrophage Harvest
2.7. Spleen Dissociation
2.8. Flow Cytometry
Reagent | Supplier | Catalog Number | Purpose | Concentration |
---|---|---|---|---|
Ficoll-Paque Plus | GE | 45-001-750 | PBMC isolation | N/A |
LPS | Sigma | Immune stimulation | 2 µg/g body weight | |
PBS | In house | N/A | PBMC isolation, FC | 1× |
K2EDTA Vacutainer | BD | 366643 | Blood collection | N/A |
FACS tubes | Fisher | FC, mouse PBMC isolation | N/A | |
Fix/Perm Kit | eBioscience | 88-8824-00 | FC | Stock |
Leucosep Tube | Grenier BioOne | 227,290P | PBMC isolation | N/A |
Syringe | Exel | 26016 | IP injection, cardiac puncture blood draw | N/A |
Isoflurane | Patterson | 07-893-8441 | Anesthesia | 1–5% |
Phagocytosis beads | Sigma | L3280 | Phagocytosis | 0.5 mL |
Legendplex | Biolegend | 740150 | Cytokine Analysis | N/A |
Specificity | Clone/Species | Conjugate | Vendor | Catalog Number | Purpose | Dilution |
---|---|---|---|---|---|---|
CD11b | M170/Rat | PerCP-Cy5.5 | Biolegend | 101,228 | FC | 1:100 |
CD45 | 30-F11/Mouse | FITC | Biolegend | 334,824 | FC | 1:200 |
CD19 | 6D5/Rat | BV605 | Biolegend | FC | 1:100 | |
CD27 | LG.3A10/Mouse | APC | Biolegend | 124,212 | FC | 1:100 |
CD3 | 17A2/Mouse | PacBlue | Biolegend | 100,214 | FC | 1:50 |
CD4 | GK1.5/Mouse | AF700 | Biolegend | 100,429 | FC | 1:50 |
CD8a | QA17A07/Mouse | SV538 | Biolegend | 155,020 | FC | 1:50 |
Ly6C | HK1.4/Rat | BV785 | Biolegend | 128,041 | FC | 1:200 |
Ly6G | 1A8/Rat | PE | Biolegend | 127,607 | FC | 1:100 |
CD11b | M1-70/Rat | FITC | Biolegend | 101,206 | FC | 1:100 |
F4/80 | BM8/Rat | AF700 | Biolegend | 123,129 | FC | 1:100 |
MHC-II | M5-114.15.2/Rat | APC-Cy7 | Biolegend | 107,602 | FC | 1:100 |
Zombie Red | N/A | N/A | Biolegend | 423,110 | FC | 1:500–1000 |
2.9. Phagocytosis
2.10. Fluorescence Minus One (FMO) Analysis
2.11. Serum Cytokine Analysis
2.12. Statistical Analysis
Equipment | Supplier | Part Number | Purpose |
---|---|---|---|
Centrifuge | Sorvall | ST8 | PBMC isolation |
Cytometer | BD | Canto II | FC |
Spectral Analyzer | Sony | SP6800 | FC |
Spectral Analyzer | Cytek | Aurora 5 L | FC |
Flow cytometer | Beckman | Cytoflex LX | FC, 13-plex ELISA |
Microcentrifuge | Fisher | 59A | FC |
3. Results
3.1. DAT Deletion Alters the Composition of the Circulating Immune System, Induces Spleen Hypoplasia, and Alters Complete Blood Count (CBC)
3.2. In DAT−/− Mice, Norepinephrine and Dopamine Levels Are Increased in Spleen and Thymus, but Not in Circulating Serum
3.3. Loss of DAT Skews the Myeloid Population to a Pro-Inflammatory Phenotype
3.4. Loss of DAT Has Divergent Effects on the Circulating Lymphoid Compartment
3.5. Memory B-Cell and CD8 T-Cells Express More DAT
3.6. Loss of DAT Alters the Peripheral Cytokine Profile
4. Discussion, Broader Biological Implications, and Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gopinath, A.; Mackie, P.M.; Phan, L.T.; Mirabel, R.; Smith, A.R.; Miller, E.; Franks, S.; Syed, O.; Riaz, T.; Law, B.K.; et al. Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses. Cells 2023, 12, 269. https://doi.org/10.3390/cells12020269
Gopinath A, Mackie PM, Phan LT, Mirabel R, Smith AR, Miller E, Franks S, Syed O, Riaz T, Law BK, et al. Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses. Cells. 2023; 12(2):269. https://doi.org/10.3390/cells12020269
Chicago/Turabian StyleGopinath, Adithya, Phillip M. Mackie, Leah T. Phan, Rosa Mirabel, Aidan R. Smith, Emily Miller, Stephen Franks, Ohee Syed, Tabish Riaz, Brian K. Law, and et al. 2023. "Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses" Cells 12, no. 2: 269. https://doi.org/10.3390/cells12020269