Sci. STKE, 16 October 2007
Inflammation Fight, Flight, or Inflame
John F. Foley
Sciences STKE, AAAS, Washington, DC 20005, USA
The catecholamines epinephrine and norepinephrine, components of the adrenergic nervous system, modulate lymphocyte proliferation and differentiation; however, their role in inflammation is unclear. Flierl et al. investigated whether macrophages and neutrophils (together called phagocytes) could serve as cellular sources of these hormones and how this might affect inflammation. The authors used enzyme-linked immunosorbant assays to show that exposure of mouse phagocytes to lipopolysaccharide (LPS) in vitro resulted in the rapid secretion of both epinephrine and norepinephrine. Real-time reverse transcription polymerase chain reaction and Western blotting assays showed that the abundance of mRNA and protein for known catecholamine-generating enzymes was increased in LPS-treated cells compared with untreated cells. The authors then studied the role of catecholamines in two animal models of lung inflammatory injury, one of which was caused by the administration of LPS. Leakage of albumin into the lung, an indicator of injury, was higher in LPS-treated mice than in control mice. Treatment of mice with an antagonist of the 2-adrenoreceptor reduced the severity of LPS-induced lung injury, as assessed by both measurement of albumin leakage and histological analysis of lung sections, whereas treatment with an 2-adrenoreceptor agonist exacerbated the damage. Blocking other adrenoreceptors had no effect on LPS-induced lung inflammation. Pharmacological blockade of sympathetic neurons indicated that they were not the source of the catecholamines; T cells were also not the source, because T cell-depleted mice still showed lung inflammation after treatment with LPS, and 2-adrenoreceptor blockade still reduced LPS-induced injury in these mice. This study identifies phagocytes as a significant source of catecholamines and raises the possibility of blocking adrenoreceptors in the treatment of inflammation.
M. A. Flierl, D. Rittirsch, B. A. Nadeau, A. J. Chen, J. V. Sarma, F. S. Zetoune, S. R. McGuire, R. P. List, D. E. Day, L. M. Hoesel, H. Gao, N. Van Rooijen, M. S. Huber-Lang, R. R. Neubig, P. A. Ward, Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature 449, 721-725 (2007). [PubMed]
Citation: J. F. Foley, Fight, Flight, or Inflame. Sci. STKE 2007, tw371 (2007).
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