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Cardiac hormones ANF and BNP modulate proliferation in the unidirectional mixed lymphocyte reaction.
J Heart Lung Transplant. 2010 Mar; 29(3):323-6.JH

Abstract

BACKGROUND

Previous investigations have shown that the plasma levels of the cardiac hormone brain natriuretic peptide (BNP) increase during acute cardiac allograft rejection as diagnosed by endomyocardial biopsy. Successful immunosuppressant treatment decreased plasma BNP levels, suggesting a role for BNP in transplantation immunity. We tested a possible immunomodulatory effect of the natriuretic peptides (NPs) BNP, atrial natriuretic factor (ANF), and C-type NP (CNP) using the unidirectional mixed lymphocyte reaction (MLR).

METHODS

Lymphocytes were isolated from the lymph nodes of Brown Norway (BN) and Lewis (L) rats. BN lymphocytes were gamma-irradiated to inhibit DNA synthesis. Lymphocytes at 2.5 x 10(6) cell/ml were mixed (at an L:BN ratio of 4:1) and incubated. On Days 2 and 3, ANF (10(-6) to 10(-11) mol/liter), BNP (10(-5) to 10(-11) mol/liter), or CNP (10(-6) to 10(-12) mol/liter) were added. Cell proliferation was measured on Day 4.

RESULTS

Reverse transcript-polymerase chain reaction (RT-PCR) analysis of BN and L lymphocytes detected NP receptor (NPR) mRNA amplicons of the expected size. MLR induced an increase in relative receptor abundance as follows: NPRA > NPRB > NPRC. ANF and BNP significantly inhibited up to approximately 50% lymphocyte proliferation in a dose-dependent manner in the range of 10(-11) to 10(-6) mol/liter, whereas CNP significantly decreased lymphocyte proliferation only modestly (approximately 20%) at 10(-8) mol/liter and at 10(-6) mol/liter.

CONCLUSIONS

Both ANF and BNP have immunomodulatory functions, although the response to cardiac rejection observed clinically involves increases in plasma levels of BNP only. This is likely related to BNP gene promoter sequences previously reported to be responsive to specific cytokines and related substances. The modulation of the MLR by NP suggests a possible clinical use of these peptides in transplantation immunity.

Authors+Show Affiliations

Cardiovascular Endocrinology Laboratory, University of Ottawa Heart Institute, Department of Medicine and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19783165

Citation

de Bold, Mercedes L Kuroski, et al. "Cardiac Hormones ANF and BNP Modulate Proliferation in the Unidirectional Mixed Lymphocyte Reaction." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 29, no. 3, 2010, pp. 323-6.
de Bold ML, Etchepare A, Martinuk A, et al. Cardiac hormones ANF and BNP modulate proliferation in the unidirectional mixed lymphocyte reaction. J Heart Lung Transplant. 2010;29(3):323-6.
de Bold, M. L., Etchepare, A., Martinuk, A., & de Bold, A. J. (2010). Cardiac hormones ANF and BNP modulate proliferation in the unidirectional mixed lymphocyte reaction. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 29(3), 323-6. https://doi.org/10.1016/j.healun.2009.07.008
de Bold ML, et al. Cardiac Hormones ANF and BNP Modulate Proliferation in the Unidirectional Mixed Lymphocyte Reaction. J Heart Lung Transplant. 2010;29(3):323-6. PubMed PMID: 19783165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac hormones ANF and BNP modulate proliferation in the unidirectional mixed lymphocyte reaction. AU - de Bold,Mercedes L Kuroski, AU - Etchepare,Alejandra, AU - Martinuk,Amy, AU - de Bold,Adolfo J, Y1 - 2009/09/26/ PY - 2009/02/05/received PY - 2009/07/16/revised PY - 2009/07/16/accepted PY - 2009/9/29/entrez PY - 2009/9/29/pubmed PY - 2010/7/7/medline SP - 323 EP - 6 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J Heart Lung Transplant VL - 29 IS - 3 N2 - BACKGROUND: Previous investigations have shown that the plasma levels of the cardiac hormone brain natriuretic peptide (BNP) increase during acute cardiac allograft rejection as diagnosed by endomyocardial biopsy. Successful immunosuppressant treatment decreased plasma BNP levels, suggesting a role for BNP in transplantation immunity. We tested a possible immunomodulatory effect of the natriuretic peptides (NPs) BNP, atrial natriuretic factor (ANF), and C-type NP (CNP) using the unidirectional mixed lymphocyte reaction (MLR). METHODS: Lymphocytes were isolated from the lymph nodes of Brown Norway (BN) and Lewis (L) rats. BN lymphocytes were gamma-irradiated to inhibit DNA synthesis. Lymphocytes at 2.5 x 10(6) cell/ml were mixed (at an L:BN ratio of 4:1) and incubated. On Days 2 and 3, ANF (10(-6) to 10(-11) mol/liter), BNP (10(-5) to 10(-11) mol/liter), or CNP (10(-6) to 10(-12) mol/liter) were added. Cell proliferation was measured on Day 4. RESULTS: Reverse transcript-polymerase chain reaction (RT-PCR) analysis of BN and L lymphocytes detected NP receptor (NPR) mRNA amplicons of the expected size. MLR induced an increase in relative receptor abundance as follows: NPRA > NPRB > NPRC. ANF and BNP significantly inhibited up to approximately 50% lymphocyte proliferation in a dose-dependent manner in the range of 10(-11) to 10(-6) mol/liter, whereas CNP significantly decreased lymphocyte proliferation only modestly (approximately 20%) at 10(-8) mol/liter and at 10(-6) mol/liter. CONCLUSIONS: Both ANF and BNP have immunomodulatory functions, although the response to cardiac rejection observed clinically involves increases in plasma levels of BNP only. This is likely related to BNP gene promoter sequences previously reported to be responsive to specific cytokines and related substances. The modulation of the MLR by NP suggests a possible clinical use of these peptides in transplantation immunity. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/19783165/Cardiac_hormones_ANF_and_BNP_modulate_proliferation_in_the_unidirectional_mixed_lymphocyte_reaction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(09)00583-X DB - PRIME DP - Unbound Medicine ER -