Phagocyte-derived catecholamines enhance acute inflammatory injury

Michael A. Flierl et al. Nature 449, 721-724 (2007).

Student: Jui-In Kai (蓋如茵)                                   Time: 14:00~15:00, May 21, 2008

Commentator: Chi-Chang Shieh (謝奇璋博士)              Place: Room 601

Abstract

Catecholamine, the major stress hormone, is derived from the amino acid tyrosine containing catechol and amine groups, such as noradrenaline and adrenaline. In addition to autonomic nervous system, catecholamines are actively produced by lymphocytes and have the capacity to act as auto- and/or paracrine regulators of lymphocyte activities, including inflammatory activation, cell proliferation, differentiation, and apoptosis [1,2]. For innate immunity, catecholamine is also a category of inflammatory mediators which acts a modulator between immune and nervous systems throughsympathetic and parasympathetic pathways [3]. To investigate the role of catecholamine in phagocytes, the authors performed in vitro experiments using isolated alveolar macrophages and blood neutrophils. Under endotoxin lipopolysaccharide (LPS) stimulation in phagocytes, results showed thede novo generation, release, and inactivation of cellular catecholamines that regulated by catecholamine-generating and degrading enzymes. To investigate the pathological effects of catecholamine, the authors performed two models of lung injury. Antagonizing a₂ adrenoceptor using selective inhibitor blocked LPS and immune complex induced the severity of experimental acute lung injury. After T-cell depletion or sympathectomy (SNSX), they excluded T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Modulating the generation of catecholamine-generating and degrading enzymes by selective inhibitors decreases or increases the severity of lung injury. Taken together, these results implies that phagocytes as a new source of catecholamines which enhances the acute inflammatory injury.

References

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2.      Musso, N. R. et al. Catecholamine content and in vitro catecholamine synthesis in peripheral human lymphocytes. Journal of Clinical Endocrinology and Metabolism 81, 3553-3557 (1996).

3.      Sternberg, E. M. et al. Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nature Review Immunology 6, 318-328 (2006).