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Norepinephrine suppresses wound macrophage phagocytic efficiency through alpha- and beta-adrenoreceptor dependent pathways

, : Norepinephrine suppresses wound macrophage phagocytic efficiency through alpha- and beta-adrenoreceptor dependent pathways. Surgery 142(2): 170-179

The systemic response to injury is characterized by massive release of norepinephrine (NE) into the circulation as a result of global sympathetic activation. We have recently demonstrated that NE modulates the recruitment of macrophages to the cutaneous wound. We hypothesized that NE suppresses wound macrophage phagocytic function through canonical adrenergic signaling pathways. Murine wound macrophages were harvested at 5 days after injury and treated with physiologic and pharmacologic dose norepinephrine. Phagocytosis of green fluorescent protein-labeled Escherichia coli was assayed by flow cytometry. The signaling pathways mediating NE modulation of wound macrophage phagocytosis were interrogated by pharmacologic manipulation of alpha- and beta-adrenoreceptors (ARs), intracellular cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). Tissue specificity was determined by comparison of wound macrophages to splenic macrophages. Both physiologic and pharmacologic dose NE suppressed wound macrophage phagocytic efficiency. This effect was mediated by alpha- and beta-ARs in a dose-dependent fashion. Direct stimulation of cAMP-suppressed phagocytic efficiency and blockade of PKA signaling prevented NE-mediated suppression of phagocytic efficiency. Splenic macrophage phagocytic efficiency was less than that of wound macrophages and was not altered by NE. NE has a profound immunosuppressive effect on wound macrophage function that is tissue specific and appears to be mediated through adrenergic receptors and their canonical downstream signaling pathway. Attenuation of post-injury immunosuppression represents another potential mechanism by which beta-AR blockade may reduce morbidity and mortality after severe injury.


PMID: 17689682

DOI: 10.1016/j.surg.2007.04.015

Other references

Yuan, Z.; Hammes, G.G., 1984: Elementary steps in the reaction mechanism of chicken liver fatty acid synthase: pH dependence of NADPH binding and isotope rate effect for b-ketoacyl reductase. The Journal of Biological Chemistry 259: 48-51

Merigan, W.H.; Nealey, T.A.; Maunsell, J.H., 1993: Visual effects of lesions of cortical area V2 in macaques. Ibotenic acid lesions were placed in two monkeys in a portion of cortical area V2 that corresponds to a lower quadrant of the visual field extending approximately 3-7 degrees from the fovea. For purposes of comparison, another lesion was placed in...

Patt R.B., 1988: The patient with pheochromocytoma. Frost, E A M (Ed ) Preanesthetic Assessment, 1 Xiv+305p Birkhauser Boston, Inc : Secaucus, New Jersey, Usa; Basel, Switzerland Illus 50-57

Park, J.Kyun.; Gelber, A.C.; George, M.; Danoff, S.K.; Qubti, M.A.; Christopher-Stine, L., 2013: Pulmonary impairment, not muscle injury, is associated with elevated ESR in the idiopathic inflammatory myopathies. Rheumatology 52(7): 1336-1338

Brandenbusch, G.; Bernauer, W., 1972: Effects of catecholamines and sympatholytics on the guinea-pig pulmonary circulation. Archives Internationales de Pharmacodynamie et de Therapie 200(1): 25-39

Sikorska Maykowska Malgorzata, 2004: Geoenvironmental map of Poland at a scale of 1:50,000; assistance in regional management and sustainable development. Przeglad Geologiczny 52(10): 1003-1004

Funk, I.G., 1961: Role of alcohol in the course of gonorrhea. Vestnik Dermatologii i Venerologii 35: 59-61

Prokudina, E.A., 1964: The functional condition of the adrenal glands in the remote periods following irradiation. White mice were given 800r Co60 gamma-irradiation. The criteria used to indicate the functional condition of the adrenal glands were the weight of the organ and the cholesterol and ascorbic acid levels. A change in the peripheral leucocyte level b...

Kokotas, H.; Petersen, M.B., 2010: Clinical and molecular aspects of aniridia. Aniridia is a severe, congenital ocular malformation inherited in an autosomal-dominant fashion with high penetrance and variable expression. Eye morphogenesis in humans involves a molecular genetic cascade in which a number of developmental genes...

Shepherd, R.E., 1977: Qualification and acceptance of container-closure systems for large volume and small volume parenterals. Bulletin of the Parenteral Drug Association 31(3): 109-113