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.


CONCLUSIONS
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.
Sookhai
S
S
Department of Surgery, Cork University Hospital, Ireland.
Wang
J H
JH
McCourt
M
M
O'Connell
D
D
Redmond
H P
HP
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D018821:CD18 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000032:analysis; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology
D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D017447:Receptors, Dopamine D1; D004298:Dopamine