1. Department of Pathology,
2. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
3. Department of Cell Biology and Immunology, Vrije Universiteit, 1081BT Amsterdam, The Netherlands
4. Department of Trauma-, Hand- and Reconstructive Surgery, University of Ulm Medical School, 89075 Ulm, Germany

Correspondence to: Peter A. Ward¹ Correspondence and requests for materials should be addressed to P.W. (Email: pward@umich.edu).

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 pathways^{1, 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 ₂-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an ₂-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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