Apoptosis is differentially regulated by burn severity and dermal location.
BACKGROUND
The cellular processes that contribute to cell death in burns are poorly understood. This study evaluated the distribution and extent of apoptosis in an established rat model of acute dermal burn injury.


METHODS
A branding iron (100 degrees C) was applied to the depilated dorsum of seven rats, creating burn contact times of 1-8, 10, 12, and 14 s. Biopsies were collected and immunohistochemistry performed for apoptosis and cell injury/necrosis by detection of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and high-mobility group box 1 (HMGB1), respectively. The slides were scored by evaluating staining in superficial, middle, and deep dermal fields. Within these, basal keratinocytes of the epidermis, mesenchymal cells, adnexal epithelia, and vasculature wall cells were morphometrically analyzed for stain detection of selected markers.


RESULTS
TUNEL staining had an inverse relationship with contact time in most fields except in deep dermal mesenchymal cells where it was increased. HMGB1 nuclear staining was significantly decreased with progressive contact time consistent with transition to cell injury/necrosis.


CONCLUSIONS
This study is the first to demonstrate that apoptosis rate is dependent on dermal location, cell type, and severity of thermal injury. Furthermore, this work suggests that for most dermal locations increased thermal injury corresponds with decreased apoptosis and increased cell injury/necrosis. Together, these findings indicate that many parameters can regulate apoptosis in burn wounds, and these results will be critical to understanding burn pathogenesis and assessing future therapies.
McNamara
Andrew R
AR
Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Zamba
Kokou D
KD
Sokolich
Julio C
JC
Jaskille
Amin D
AD
Light
Timothy D
TD
Griffin
Michelle A
MA
Meyerholz
David K
DK
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D002056:Burns / Q000473:pathology*; D005263:Femoral Artery / Q000473:pathology; D024243:HMGB1 Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012867:Skin / Q000473:pathology*; D014947:Wounds and Injuries / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat