Local Burn Injury Promotes Defects in the Epidermal Lipid and Antimicrobial Peptide Barriers in Human Autograft Skin and Burn Margin

Abstract

Burn injury increases the risk of morbidity and mortality by promoting severe hemodynamic shock and risk for local or systemic infection. Graft failure due to poor wound healing or infection remains a significant problem for burn subjects. The mechanisms by which local burn injury compromises the epithelial antimicrobial barrier function in the burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue, are largely unknown. The objective of this study was to establish defects in epidermal barrier function in human donor skin and burn margin, in order to identify potential mechanisms that may lead to graft failure and/or impaired burn wound healing. In the present study, we established that epidermal lipids and respective lipid synthesis enzymes were significantly reduced in both donor skin and burn margin. We further identified diverse changes in the gene expression and protein production of several candidate skin antimicrobial peptides (AMPs) in both donor skin and burn margin. These results also parallel changes in cutaneous AMP activity against common burn wound pathogens, aberrant production of epidermal proteases known to regulate barrier permeability and AMP activity, and greater production of pro-inflammatory cytokines known to be induced by AMPs. These findings suggest that impaired epidermal lipid and AMP regulation could contribute to graft failure and infectious complications in subjects with burn or other traumatic injury.

Burn Injury Alters Epidermal Cholinergic Mediators and Increases HMGB1 and Caspase 3 in Autologous Donor Skin and Burn Margin

“…Patient characteristics that represent the general population treated in the Loyola BICU have been previously described (24). In brief, patient ages ranged from 20 to 87 years (mean 47 years, median 46 years).…”

“…Patients admitted to the Burn Intensive Care Unit (BICU) were excluded from the study under the following criteria: age < 18 years, pre-existing skin disease, previous transplant recipient, pre-existing clinically-evident infection, history of disseminated cancer, major traumatic injury <4 months prior to the burn injury, and/or pre-existing immunodeficiency. The percent total body surface area (% TBSA) of burn, and fluid resuscitation have been previously described (24), and are summarized in Table 1. The following clinical characteristics and outcomes were obtained from the electronic medical records and were entered into a database: age, gender, burn injury mechanism, % TBSA, inhalation injury, wound infection, graft failure, pneumonia, urinary tract infection, sepsis and/or multisystem organ dysfunction (MODS), and mortality.…”

“…A sham burn was performed using the cautery device at ambient temperatures (no heat; device in the “off” position). Cells treated with the sham burn were used as controls for these experiments, rather than distal cells in the wells that were subjected to burn injury, because we previously determined that burn injury in humans elicits skin barrier defects in distal unburned skin (24). Thus, unburned control cells were deemed a more appropriate cohort for these studies.…”

Cutaneous Burn Injury Promotes Shifts in the Bacterial Microbiome in Autologous Donor Skin

“…protein levels and activity) are impaired in both donor skin and burn margin from human burn patients, which likely influences, or is influenced by, changes in the resident skin microbiota (12). Several skin pathogens ( e.g.…”

“…Burn wound infection at both the donor and burn site remain a frequent and serious complication of major burn injury and account for over 50% of all deaths related to burn injury (6, 10, 11). We recently determined that epidermal lipid and antimicrobial peptide (AMP) responses are impaired in both donor skin and burn margin from human burn patients (12). These alterations in epidermal barrier function demonstrate that traumatic burn injury elicits a global change in the antimicrobial function of presumably normal skin, which would serve as donor skin for burn patients.…”