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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 5, November, 2001 636-643

Modulation of Chemokine Production in Lung Microvascular Endothelial Cells by Dopamine Is Mediated via an Oxidative Mechanism

Grietje Ch. Beck, Ralph Oberacker, Silke Kapper, Detlef von Zabern, Jutta Schulte, Klaus van Ackern, Fokko J. van der Woude, and Benito A. Yard

Institute for Anaesthesiology, and the V. Medical Clinic, University of Mannheim, Mannheim, Germany

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 µg/ml) or lipoteichonic acid (LTA) (10 µg/ml) in the presence or absence of various concentrations of DA (1-100 µg/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 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.

Abbreviations: acute respiratory distress syndrome, ARDS; dopamine, DA; epithelial neutrophil activating protein-78, ENA-78; growth-related gene alpha , Gro-alpha ; heme oxygenase 1, HO-1; interleukin-8, IL-8; lung microvascular endothelial cells, LMVEC; lipopolysaccharide, LPS; lipoteichonic acid, LTA; monoamine oxidase, MOA; N-acetylcysteine, NAC; polymerase chain reaction, PCR; reactive oxygen species, ROS.




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