Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension
IntroductionDepletion 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 e...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1184982/full |
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| author | Hericka Bruna Figueiredo Galvao Quynh Nhu Dinh Jordyn M. Thomas Flavia Wassef Henry Diep Alex Bobik Alex Bobik Alex Bobik Christopher G. Sobey Christopher G. Sobey Grant R. Drummond Grant R. Drummond Antony Vinh |
| author_facet | Hericka Bruna Figueiredo Galvao Quynh Nhu Dinh Jordyn M. Thomas Flavia Wassef Henry Diep Alex Bobik Alex Bobik Alex Bobik Christopher G. Sobey Christopher G. Sobey Grant R. Drummond Grant R. Drummond Antony Vinh |
| author_sort | Hericka Bruna Figueiredo Galvao |
| collection | DOAJ |
| description | IntroductionDepletion 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.MethodsMale 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 (CD138hiSca-1+Blimp-1+) were enumerated by flow cytometry. Serum immunoglobulins were quantified using a bead-based immunoassay.ResultsBortezomib treatment reduced splenic ASCs by ∼68% and ∼64% compared to vehicle treatment in normotensive (2.00 ± 0.30 vs. 0.64 ± 0.15 × 105 cells; n = 10–11) and hypertensive mice (0.52 ± 0.11 vs. 0.14 ± 0.02 × 105 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 × 103 cells; n = 9–11) and hypertensive mice (4.12 ± 0.82 vs. 0.89 ± 0.18 × 103 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).ConclusionReductions 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. |
| first_indexed | 2024-03-13T07:55:19Z |
| format | Article |
| id | doaj.art-9c1030f86c7b434f860c0dea7c447266 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-03-13T07:55:19Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-9c1030f86c7b434f860c0dea7c4472662023-06-02T06:09:06ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-06-011010.3389/fcvm.2023.11849821184982Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertensionHericka Bruna Figueiredo Galvao0Quynh Nhu Dinh1Jordyn M. Thomas2Flavia Wassef3Henry Diep4Alex Bobik5Alex Bobik6Alex Bobik7Christopher G. Sobey8Christopher G. Sobey9Grant R. Drummond10Grant R. Drummond11Antony Vinh12Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, AustraliaBiomedicine Discovery Institute, Monash University, Melbourne, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, AustraliaBaker Heart and Diabetes Institute, Prahran, AustraliaDepartment of Immunology, Monash University, Melbourne, VIC, AustraliaCentre for Inflammatory Diseases, Monash University, Clayton, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, AustraliaBaker Heart and Diabetes Institute, Prahran, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, AustraliaBaker Heart and Diabetes Institute, Prahran, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, AustraliaIntroductionDepletion 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.MethodsMale 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 (CD138hiSca-1+Blimp-1+) were enumerated by flow cytometry. Serum immunoglobulins were quantified using a bead-based immunoassay.ResultsBortezomib treatment reduced splenic ASCs by ∼68% and ∼64% compared to vehicle treatment in normotensive (2.00 ± 0.30 vs. 0.64 ± 0.15 × 105 cells; n = 10–11) and hypertensive mice (0.52 ± 0.11 vs. 0.14 ± 0.02 × 105 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 × 103 cells; n = 9–11) and hypertensive mice (4.12 ± 0.82 vs. 0.89 ± 0.18 × 103 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).ConclusionReductions 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.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1184982/fullhypertensionbortezomibantibody secreting cellsimmunoglobulinsangiotensin IIproteasome inhibition |
| spellingShingle | Hericka Bruna Figueiredo Galvao Quynh Nhu Dinh Jordyn M. Thomas Flavia Wassef Henry Diep Alex Bobik Alex Bobik Alex Bobik Christopher G. Sobey Christopher G. Sobey Grant R. Drummond Grant R. Drummond Antony Vinh Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension Frontiers in Cardiovascular Medicine hypertension bortezomib antibody secreting cells immunoglobulins angiotensin II proteasome inhibition |
| title | Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension |
| title_full | Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension |
| title_fullStr | Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension |
| title_full_unstemmed | Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension |
| title_short | Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced hypertension |
| title_sort | proteasome inhibition reduces plasma cell and antibody secretion but not angiotensin ii induced hypertension |
| topic | hypertension bortezomib antibody secreting cells immunoglobulins angiotensin II proteasome inhibition |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1184982/full |
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