Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension.
| Autor: | Figueiredo Galvao HB; Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia., Dinh QN; Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia., Thomas JM; Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia., Wassef F; Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia., Diep H; Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia., Bobik A; Baker Heart and Diabetes Institute, Prahran, Australia.; Department of Immunology, Monash University, Melbourne, VIC, Australia.; Centre for Inflammatory Diseases, Monash University, Clayton, VIC, Australia., Sobey CG; Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.; Baker Heart and Diabetes Institute, Prahran, Australia., Drummond GR; Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.; Baker Heart and Diabetes Institute, Prahran, Australia., Vinh A; Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2023 Jun 02; Vol. 10, pp. 1184982. Date of Electronic Publication: 2023 Jun 02 (Print Publication: 2023). |
| DOI: | 10.3389/fcvm.2023.1184982 |
| Abstrakt: | Introduction: Depletion of mature B cells affords protection against experimental hypertension. However, whether B cell-mediated hypertension is dependent on differentiation into antibody-secreting cells (ASCs) remains unclear. Using the proteasome inhibitor, bortezomib, the present study tested the effect of ASC reduction on angiotensin II-induced hypertension. Methods: Male C57BL6/J mice were infused with angiotensin II (0.7 mg/kg/day; s.c.) for 28 days via osmotic minipump to induce hypertension. Normotensive control mice received saline infusion. Bortezomib (750 μg/kg) or vehicle (0.1% DMSO) was administered (i.v.) 3 days prior to minipump implantation, and twice weekly thereafter. Systolic blood pressure was measured weekly using tail-cuff plethysmography. Spleen and bone marrow B1 (CD19 + B220 - ), B2 (B220 + CD19 + ) and ASCs (CD138 hi Sca-1 + Blimp-1 + ) were enumerated by flow cytometry. Serum immunoglobulins were quantified using a bead-based immunoassay. Results: Bortezomib treatment reduced splenic ASCs by ∼68% and ∼64% compared to vehicle treatment in normotensive (2.00 ± 0.30 vs. 0.64 ± 0.15 × 10 5 cells; n = 10-11) and hypertensive mice (0.52 ± 0.11 vs. 0.14 ± 0.02 × 10 5 cells; n = 9-11), respectively. Bone marrow ASCs were also reduced by bortezomib in both normotensive (4.75 ± 1.53 vs. 1.71 ± 0.41 × 10 3 cells; n = 9-11) and hypertensive mice (4.12 ± 0.82 vs. 0.89 ± 0.18 × 10 3 cells; n = 9-11). Consistent with ASC reductions, bortezomib reduced serum IgM and IgG2a in all mice. Despite these reductions in ASCs and antibody levels, bortezomib did not affect angiotensin II-induced hypertension over 28 days (vehicle: 182 ± 4 mmHg vs. bortezomib: 177 ± 7 mmHg; n = 9-11). Conclusion: Reductions in ASCs and circulating IgG2a and IgM did not ameliorate experimental hypertension, suggesting other immunoglobulin isotypes or B cell effector functions may promote angiotensin II-induced hypertension. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Figueiredo Galvao, Dinh, Thomas, Wassef, Diep, Bobik, Sobey, Drummond and Vinh.) |
| Databáze: | MEDLINE |
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