Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism

Background. For the normal resolution of an acute inflammatory response, ne utrophil (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 syndro me (SIRS). Dopamine, a biogenic amine with known cardiovascular and neurotr ansmitter properties, is used in patients with SIRS to maintain hemodynamic stability. We sought to determine whether dopamine may also have immunoreg ulatory properties capable of influencing PMN apoptosis, function, and acti vation 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 agon ist, fenoldopam. PMN apoptosis was assessed every 6 hours with use of propi dium iodide DNA staining and PMN function was assessed with use of respirat ory burst activity, phagocytosis ability, and CD11a, CD11b, and CD18 recept or expression as functional markers. Results. There was a significant delay in PMN apotosis in patients with SIR S compared with controls. Treatment of isolated PMNs from both healthy cont rols and patients with SIRS with 10 and 100 mu mol/L dopamine induced apopt osis. PMN ingestive and cytocidal capacity were both decreased in patients with SIRS compared with controls. Treatment with dopamine significantly inc reased phagocytic function. Fenoldopam did not induce PMN apoptosis. Conclusion. Our data demonstrate for the first time that dopamine induces P MN apoptosis and modulates PMN function both in healthy controls and in pat ients with SIRS. These results indicate that dopamine may be beneficial dur ing SIRS through a nonhemodynamic PMN-dependent proapoptotic mechanism.