Modulation of chemokine production in lung microvascular endothelial cells by dopamine is mediated via an oxidative mechanism

Serum concentrations of catecholamines are high in patients with sepsis
or acute respiratory distress syndrome (ARDS). Because chemokines
mediate the recruitment of neutrophils into inflammatory sites, we
addressed the question of whether dopamine (DA) is able to influence
chemokine production in endothelial cells under basal and
proinflammatory conditions. To this end, lung microvascular endothelial
cells (LMVEC) were stimulated or not for 24 h with the bacterial toxins
lipopolysaccharide (LPS) (1 mug/ml) or lipoteichonic acid (LTA) (10
mug/ml) in the presence or absence of various concentrations of DA
(1-100 mug/ml). Whereas under basal and stimulatory conditions, the
addition of DA to endothelial cells dose-dependently increased IL-8
production, the production of ENA-78 and Gro-alpha was significantly
inhibited (P < 0.01). This effect could still be demonstrated when the
cells were stimulated for up to 3 h with LPS before DA administration.
Similar findings were detected for the mRNA expression of these
chemokines. The influence of DA on chemokine production was not
receptor mediated and could be prevented by antioxidants or radical
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scavengers. Moreover, addition of H2O2 to endothelial cells gave
results similar to those observed with DA stimulation, suggesting a
pivotal role for reactive oxygen species in DA-mediated modulation of
chemokine production in endothelial cells. Our data thus demonstrate
that DA administration results in the induction of oxidative stress,
with profound effects on endothelial chemokine production.