Local Burn Injury Impairs Epithelial Permeability and Antimicrobial Peptide Barrier Function in Distal Unburned Skin Journal Article

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Authors: Plichta, J. K.; Droho, S.; Curtis, B. J.; Patel, P; Gamelli, R. L.; Radek, K. A.
Article Title: Local Burn Injury Impairs Epithelial Permeability and Antimicrobial Peptide Barrier Function in Distal Unburned Skin
Abstract: OBJECTIVES:: 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. DESIGN:: Experimental mouse scald burn injury. SETTING:: University Research Laboratory. SUBJECTS:: C57/Bl6 Male mice, 8-12 weeks old. INTERVENTIONS:: 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. MEASUREMENTS AND MAIN 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.
Journal Title: Critical Care Medicine
Volume: 42
Issue: 6
ISSN: 1530-0293; 0090-3493
Publisher: Unknown  
Date Published: 2014
Start Page: e420
End Page: 431
Language: ENG
DOI/URL:

10.1097/CCM.0000000000000309
Notes: LR: 20141120; GR: T32 AA013527/AA/NIAAA NIH HHS/United States; GR: T32 GM008750/GM/NIGMS NIH HHS/United States; GR: T32-5T32AA013527-09/AA/NIAAA NIH HHS/United States; GR: T32-GM008750-11/GM/NIGMS NIH HHS/United States; JID: 0355501; 0 (Antimicrobial Cationic Peptides); 0 (Membrane Lipids); EC 3.4.- (Peptide Hydrolases); CIN: Crit Care Med. 2014 Jun;42(6):1575-7. PMID: 24836807; NIHMS640614; OID: NLM: NIHMS640614; OID: NLM: PMC4231880; ppublish