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Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro
Published on: January 25, 2017
Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism
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.
Insights
Dopamine induces neutrophil apoptosis and improves their function in patients with systemic inflammatory response syndrome (SIRS). This suggests dopamine offers benefits beyond hemodynamic support by influencing neutrophil behavior.
Area of Science:
- Immunology
- Pharmacology
Background:
- Neutrophil (PMN) apoptosis is crucial for resolving inflammation and maintaining immune homeostasis.
- Delayed PMN apoptosis is linked to the pathogenesis of systemic inflammatory response syndrome (SIRS).
- Dopamine, used for hemodynamic stability in SIRS, may possess immunomodulatory effects.
Purpose of the Study:
- To investigate dopamine's influence on PMN apoptosis, function, and activation in SIRS patients.
- To determine if dopamine has immunoregulatory properties affecting neutrophils.
Main Methods:
- Isolated PMNs from healthy volunteers and SIRS patients were treated with dopamine and fenoldopam.
- PMN apoptosis was measured using propidium iodide DNA staining.
- PMN function was assessed via respiratory burst, phagocytosis, and receptor expression (CD11a, CD11b, CD18).
Main Results:
- SIRS patients exhibited delayed PMN apoptosis compared to controls.
- Dopamine treatment (10-100 µmol/L) induced apoptosis in PMNs from both groups.
- Dopamine enhanced phagocytic function, while fenoldopam did not induce apoptosis.
Conclusions:
- Dopamine induces PMN apoptosis and modulates PMN function in both healthy individuals and SIRS patients.
- Dopamine may provide therapeutic benefits in SIRS via a non-hemodynamic, PMN-dependent proapoptotic mechanism.
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