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

Ankush Gosain, Kuzhali Muthu, Richard L. Gamelli, Luisa A. DiPietro

Research output: Contribution to journalArticle

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Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)170-179
Number of pages10
JournalSurgery
Volume142
Issue number2
DOIs
StatePublished - Aug 1 2007

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Norepinephrine
Macrophages
Wounds and Injuries
Cyclic AMP-Dependent Protein Kinases
Phagocytosis
Adenosine Kinase
Organ Specificity
Immunosuppressive Agents
Green Fluorescent Proteins
Cyclic AMP
Adrenergic Agents
Immunosuppression
Adrenergic Receptors
Flow Cytometry
Escherichia coli
Morbidity
Skin
Mortality

All Science Journal Classification (ASJC) codes

  • Surgery

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Norepinephrine suppresses wound macrophage phagocytic efficiency through alpha- and beta-adrenoreceptor dependent pathways. / Gosain, Ankush; Muthu, Kuzhali; Gamelli, Richard L.; DiPietro, Luisa A.

In: Surgery, Vol. 142, No. 2, 01.08.2007, p. 170-179.

Research output: Contribution to journalArticle

Gosain, Ankush ; Muthu, Kuzhali ; Gamelli, Richard L. ; DiPietro, Luisa A. / Norepinephrine suppresses wound macrophage phagocytic efficiency through alpha- and beta-adrenoreceptor dependent pathways. In: Surgery. 2007 ; Vol. 142, No. 2. pp. 170-179.
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