Abstract/Details

Norepinephrine modulates wound neutrophil and macrophage phagocytic efficiency


2006 2006

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Abstract (summary)

Trauma is the leading killer of Americans 1-44 years old and results in more years of potential life lost than any other disease process. The incidence of infectious complications, both systemic and local, is markedly increased following trauma and sepsis accounts for the majority of deaths after the initial 48 hours post-injury. A growing body of literature supports the concept of neuroimmunomodulation, or nervous system modulation of immune function. Following severe injury there is destruction of noradrenergic neurons innervating the injured tissue and massive release of norepinephrine into the peripheral circulation. Alterations in the post-trauma catecholamine milieu are often compounded by the clinical use of vasopressor agents for hemodynamic support.

Neutrophils and macrophages play a critical role in successful tissue repair as key mediators of the inflammatory phase of wound healing. Following their recruitment to the site of injury, these innate immune cells function in phagocytosis and the production of growth factors and cytokines to coordinate wound repair. Additionally, through the process of phagocytosis, neutrophils and macrophages perform an antimicrobial innate immune function and link to the adaptive immune response through antigen presentation.

We have demonstrated that, following massive release of norepinephrine and tissue level depletion, there is a decrease in recruited neutrophils and a delay in recruited macrophages in the cutaneous wound. Furthermore, during the period of tissue repair, rising norepinephrine levels suppress wound neutrophil and macrophage phagocytic efficiency. Our results also indicate that this effect is mediated by the α- and β-adrenergic receptors via intracellular cyclic AMP and PKA in a dose-defined fashion. Taken as a whole, these events combine to produce a marked derangement in innate immunity at the level of the cutaneous wound and may provide an opportunity for pathogens to gain entry to the host.

Indexing (details)


Subject
Cellular biology;
Immunology
Classification
0379: Cellular biology
0982: Immunology
Identifier / keyword
Health and environmental sciences; Biological sciences; Macrophages; Neutrophil; Norepinephrine; Phagocytic; Wound
Title
Norepinephrine modulates wound neutrophil and macrophage phagocytic efficiency
Author
Gosain, Ankush
Number of pages
137
Publication year
2006
Degree date
2006
School code
0112
Source
DAI-B 68/01, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
Advisor
Dipietro, Luisa A.
University/institution
Loyola University Chicago
University location
United States -- Illinois
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3244824
ProQuest document ID
305318872
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305318872
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