Local burn injury impairs epithelial permeability and antimicrobial peptide barrier function in distal unburned skin.
OBJECTIVE
Our objective was to characterize the mechanisms by which local burn injury compromises epithelial barrier function in burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue.


METHODS
Experimental mouse scald burn injury.


METHODS
University Research Laboratory.


METHODS
C57/Bl6 Male mice, 8-12 weeks old.


METHODS
To confirm that dehydration was not contributing to our observed barrier defects, in some experiments mice received 1 mL of saline fluid immediately after burn, while a subgroup received an additional 0.5 mL at 4 hours and 1 mL at 24 hours following burn. We then assessed skin pH and transepidermal water loss every 12 hours on the burn wounds for 72 hours postburn.


RESULTS
Burn margin exhibited increased epidermal barrier permeability indicated by higher pH, greater transepidermal water loss, and reduced lipid synthesis enzyme expression and structural protein production up to 96 hours postburn. By contrast, antimicrobial peptide production and protease activity were elevated in burn margin. Skin extracts from burn margin did not exhibit changes in the ability to inhibit bacterial growth. However, distal unburned skin from burned mice also demonstrated an impaired response to barrier disruption, indicated by elevated transepidermal water loss and reduced lipid synthesis enzyme and structural protein expression up to 96 hours postburn. Furthermore, skin extracts from distal unburned skin exhibited greater protease activity and a reduced capacity to inhibit bacterial growth of several skin pathogens. Finally, we established that antimicrobial peptide levels were also altered in the lung and bladder, which are common sites of secondary infection in burn-injured patients.


CONCLUSIONS
These findings reveal several undefined deficiencies in epithelial barrier function at the burn margin, potential donor skin sites, and organs susceptible to secondary infection. These functional and biochemical data provide novel insights into the mechanisms for graft failure and secondary infection after burn injury.
1Department of Surgery, Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Division, Maywood, IL. 2Department of Surgery, Loyola University Chicago, Health Sciences Division, Maywood, IL.
Jennifer K
JK
Plichta
Steve
S
Droho
Brenda J
BJ
Curtis
Parita
P
Patel
Richard L
RL
Gamelli
Katherine A
KA
Radek
D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001424:Bacterial Infections / Q000209:etiology; D002056:Burns / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D003681:Dehydration; D004817:Epidermis / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010447:Peptide Hydrolases / Q000378:metabolism*; D010539:Permeability; D016133:Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D014945:Wound Healing / Q000276:immunology / Q000502:physiology*
D023181:Antimicrobial Cationic Peptides; D008563:Membrane Lipids; D010447:Peptide Hydrolases