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Phagocyte-derived catecholamines enhance acute inflammatory injury

Abstract

It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways1,2. We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes3. Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines. To assess the importance of these findings in vivo, we chose two models of acute lung injury. Blockade of α2-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an α2-adrenoreceptor agonist or for inhibition of catecholamine-degrading enzymes. We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response.

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Figure 1: Release of catecholamines from phagocytes and the presence of catecholamine-producing enzymes in phagocytes.
Figure 2: Expression of catecholamine-inactivating enzymes in phagocytes.
Figure 3: The α 2 -adrenoceptor mediates the severity of experimental acute lung injury.
Figure 4: Phagocyte-derived catecholamines mediate lung injury.

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Acknowledgements

We thank B. Schumann and S. Scott for assistance in the preparation of this manuscript. This study was supported by NIH grants to P.A.W. and R.R.N., and by Deutsche Forschungsgemeinschaft grants to M.S.H.-L.

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Correspondence to Peter A. Ward.

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Flierl, M., Rittirsch, D., Nadeau, B. et al. Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature 449, 721–725 (2007). https://doi.org/10.1038/nature06185

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