Phagocyte-derived catecholamines enhance acute inflammatory injury
| Autor: | Rachel P. List, Hongwei Gao, Nico van Rooijen, Daniel Rittirsch, L. Marco Hoesel, Richard R. Neubig, J. Vidya Sarma, Firas S. Zetoune, Stephanie R. McGuire, Brian A. Nadeau, Markus Huber-Lang, Peter A. Ward, A. Chen, Michael A. Flierl, Danielle E. Day |
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| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Lung Diseases Male Lipopolysaccharide Phagocyte Neutrophils T-Lymphocytes Inflammation Biology Lung injury chemistry.chemical_compound Catecholamines Immune system Receptors Adrenergic alpha-2 medicine Animals Rats Long-Evans Phagocytes Multidisciplinary Macrophages Adrenergic alpha-2 Receptor Antagonists Immune complex Rats Autonomic nervous system medicine.anatomical_structure chemistry Acute Disease Immunology medicine.symptom Adrenal medulla |
| Zdroj: | Nature. 449:721-725 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature06185 |
| Popis: | The discovery that phagocytic blood cells (macrophages and neutrophils) are a significant source of catecholamines (noradrenaline and adrenaline), and can cause reinforcement of the acute inflammatory response, comes as a surprise. The body's inflammatory response to traumatic injury or infection is designed to protect it and return it to the preinjury state, but excessive inflammatory responses can seriously injure tissues and organs. Experiments in rat and mouse models of acute lung injury show that phagocytes act as virtually a third component of the adrenergic system — joining the adrenal medulla in the brain, and synaptic neurons. The findings raise the possibility that unwanted inflammatory responses (as seen in atherosclerosis, acute cardiac ischaemic injury and acute lung injury) might be suppressed in humans by adrenoreceptor blockade. Macrophages and neutrophils release catecholamines after exposure to lipopolysaccharide or immune complex stimulation, and phagocyte-derived catecholamines contribute to acute lung injury. 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. |
| Databáze: | OpenAIRE |
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