Norepinephrine-Mediated Suppression of Phagocytosis by Wound Neutrophils

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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. Multiple authors have demonstrated NE-mediated alterations in migration of circulating neutrophils to wounds. We hypothesized that NE further alters wound neutrophil phagocytic function through adrenergic signaling pathways. Methods: A standard subcutaneous sponge wound model was used. Murine wound neutrophils were harvested at 24 and 120 h after injury and treated with physiological (10-9 M) and pharmacologic (10-6 M) doses of NE. Phagocytosis of green fluorescent protein-labeled Escherichia coli was assayed by flow cytometry. The signaling pathways mediating NE modulation of phagocytosis by wound neutrophils were defined by pharmacologic manipulation of α- and β-adrenoreceptors and protein kinase A. Results: Pharmacologic-dose NE, but not-physiological-dose NE, suppressed the phagocytic efficiency of 120-h wound neutrophils. This alteration in phagocytic efficiency appears to be mediated through alpha- and beta- adrenorecptors and downstream protein kinase A. Phagocytosis by 24-h wound neutrophils was not impacted by NE treatment. Conclusions: The present study is the first to demonstrate NE-mediated alterations in the process of phagocytosis by wound neutrophils. We conclude that NE plays a temporally and dose-defined immunomodulatory role in cutaneous wound healing through alterations in phagocytosis by wound neutrophils and may represent a target for therapeutic manipulation of the innate immune response.

Original languageEnglish (US)
Pages (from-to)311-318
Number of pages8
JournalJournal of Surgical Research
Volume152
Issue number2
DOIs
StatePublished - Apr 1 2009

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Phagocytosis
Norepinephrine
Neutrophils
Wounds and Injuries
Cyclic AMP-Dependent Protein Kinases
Porifera
Green Fluorescent Proteins
Innate Immunity
Adrenergic Agents
Wound Healing
Flow Cytometry
Escherichia coli
Skin

All Science Journal Classification (ASJC) codes

  • Surgery

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Norepinephrine-Mediated Suppression of Phagocytosis by Wound Neutrophils. / Gosain, Ankush; Gamelli, Richard L.; DiPietro, Luisa A.

In: Journal of Surgical Research, Vol. 152, No. 2, 01.04.2009, p. 311-318.

Research output: Contribution to journalArticle

Gosain, Ankush ; Gamelli, Richard L. ; DiPietro, Luisa A. / Norepinephrine-Mediated Suppression of Phagocytosis by Wound Neutrophils. In: Journal of Surgical Research. 2009 ; Vol. 152, No. 2. pp. 311-318.
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