Norepinephrine modulates the inflammatory and proliferative phases of wound healing.
BACKGROUND
Injury results in the massive release of norepinephrine (NE) into the peripheral circulation. Recent investigations have demonstrated functional adrenoreceptors on the cellular mediators of cutaneous wound healing and NE-induced phenotypic alterations in immune cells have been demonstrated in vitro. Despite this, there is little description of how NE might alter the phases of wound healing in vivo. The purpose of this study was to compare cutaneous wound healing in norepinephrine-intact and norepinephrine-depleted mice.


METHODS
Norepinephrine-depleted (NED) mice were generated by chemical axotomy with 6-hydroxydopamine and compared with norepinephrine-intact (NEI) animals (n = 6-12 per group, per time point). Using an excisional wound model, neutrophil recruitment was measured by myeloperoxidase assay. Macrophage recruitment and angiogenesis were measured by immunohistochemistry and re-epithelialization was determined histologically. The development of incisional wound disruption strength was determined over time. Finally, macrophage scavenger function was assessed by an in vitro latex bead phagocytosis assay.


RESULTS
Wounds from NEI mice demonstrated greater neutrophil infiltration than NED wounds (24, 72 hours; p < 0.05). Wound macrophage recruitment was initially higher in NEI animals (24 hours, p < 0.05), but was eventually surpassed by that of NED animals (120 hours, p < 0.05). Angiogenesis was decreased while re-epithelialization was accelerated in NEI animals (p < 0.05). Wound disruption strength and macrophage scavenger function were unaltered between NED and NEI mice.


CONCLUSIONS
Norepinephrine modulates the inflammatory and proliferative phases of wound healing in a temporally defined, cell-specific manner. By increasing recruitment of innate immune cells and expediting wound closure, norepinephrine appears to play a protective role in defense against infection.
Gosain
Ankush
A
Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, IL 60153, USA.
Jones
Stephen B
SB
Shankar
Ravi
R
Gamelli
Richard L
RL
DiPietro
Luisa A
LA
D000818:Animals; D005260:Female; D007249:Inflammation / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D013566:Sympathomimetics; D009638:Norepinephrine