Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism.
Sookhai, S Wang, J H McCourt, M O'Connell, D Redmond, H P
Sookhai, S
Wang, J H
McCourt, M
O'Connell, D
Redmond, H P
Advisors
Editors
Other Contributors
Date
2012-02-03T15:13:27Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adult
Aged
Antigens, CD18/analysis
Apoptosis/*drug effects
Cytotoxicity, Immunologic/drug effects
Dopamine/*pharmacology
Humans
Macrophage-1 Antigen/analysis
Middle Aged
Neutrophils/*drug effects/immunology
Receptors, Dopamine D1/*physiology
Systemic Inflammatory Response Syndrome/immunology
Aged
Antigens, CD18/analysis
Apoptosis/*drug effects
Cytotoxicity, Immunologic/drug effects
Dopamine/*pharmacology
Humans
Macrophage-1 Antigen/analysis
Middle Aged
Neutrophils/*drug effects/immunology
Receptors, Dopamine D1/*physiology
Systemic Inflammatory Response Syndrome/immunology
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
BACKGROUND: For the normal resolution of an acute inflammatory response, neutrophil (PMN) apoptosis is essential to maintain immune homeostasis and to limit inappropriate host tissue damage. A delay in PMN apoptosis has been implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS). Dopamine, a biogenic amine with known cardiovascular and neurotransmitter properties, is used in patients with SIRS to maintain hemodynamic stability. We sought to determine whether dopamine may also have immunoregulatory properties capable of influencing PMN apoptosis, function, and activation state in patients with SIRS. METHODS: PMNs were isolated from healthy volunteers and patients with SIRS and treated with varying doses of dopamine and a dopamine D-1 receptor agonist, fenoldopam. PMN apoptosis was assessed every 6 hours with use of propidium iodide DNA staining and PMN function was assessed with use of respiratory burst activity, phagocytosis ability, and CD11a, CD11b, and CD18 receptor expression as functional markers. RESULTS: There was a significant delay in PMN apotosis in patients with SIRS compared with controls. Treatment of isolated PMNs from both healthy controls and patients with SIRS with 10 and 100 mumol/L dopamine induced apoptosis. PMN ingestive and cytocidal capacity were both decreased in patients with SIRS compared with controls. Treatment with dopamine significantly increased phagocytic function. Fenoldopam did not induce PMN apoptosis. CONCLUSION: Our data demonstrate for the first time that dopamine induces PMN apoptosis and modulates PMN function both in healthy controls and in patients with SIRS. These results indicate that dopamine may be beneficial during SIRS through a nonhemodynamic PMN-dependent proapoptotic mechanism.
Language
eng
Citation
ISSN
0039-6060 (Print)
0039-6060 (Linking)
0039-6060 (Linking)
eISSN
ISBN
DOI
PMID
10455900