title: Caspase-3-dependent organ apoptosis early after burn injury.
abstract: OBJECTIVE
  To examine the role played by endotoxin, tumor necrosis factor-alpha (TNF-alpha), and caspase-3 in the increased apoptosis seen in solid organs in the early period after a burn injury.
  
  
  BACKGROUND
  Burn injury is often associated with immune suppression. Bacterial translocation and systemic endotoxemia have been reported after a burn injury, and caspase-3 activation due to TNF-alpha and Fas ligand (FasL) are presumed to initiate apoptosis. We hypothesized that endotoxin-induced TNF-alpha expression and caspase-3 activation could be the stimulus for the apoptosis after burn injury.
  
  
  METHODS
  A 20% full-thickness scald burn was used in C57BL/6 mice. Three hours after burn injury, tissue samples were obtained from the thymus, lung, liver, and spleen. Lipopolysaccharide-nonresponsive (C3H/HeJ) and TNFalpha null B6x129tnf-/- mice were also used. To detect apoptosis, hematoxylin and eosin stain, in situ TUNEL, DNA extraction, and gel electrophoresis were all performed. Caspase-3 activity and TNF-alpha and FasL mRNA were also measured.
  
  
  RESULTS
  Increased apoptosis and caspase-3 activity were observed in the thymus and spleen 3 hours after burn injury but were not seen in liver or lung. In the thymus and spleen, increased expression of FasL mRNA was also observed, whereas increased TNF-alpha mRNA was not. Increased apoptosis in thymus and spleen were also observed in C3H/HeJ and B6x129tnf-/- mice after burn injury. An inhibitor of the caspase-3 (Z-VAD-fmk) reduced apoptosis in both thymus and spleen.
  
  
  CONCLUSIONS
  In the early period after a burn injury, increased apoptosis is observed primarily in the lymphoid organs and is independent of endotoxin or TNF-alpha. The increased caspase-3 activity in thymus and spleen contributes to apoptosis in these organs.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville 32606-0286, USA.
authors.forename: K
authors.initials: K
authors.lastname: Fukuzuka
authors.forename: J J
authors.initials: JJ
authors.lastname: Rosenberg
authors.forename: G C
authors.initials: GC
authors.lastname: Gaines
authors.forename: C K
authors.initials: CK
authors.lastname: Edwards
authors.forename: M
authors.initials: M
authors.lastname: Clare-Salzler
authors.forename: S L
authors.initials: SL
authors.lastname: MacKay
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: E M
authors.initials: EM
authors.lastname: Copeland
authors.forename: D W
authors.initials: DW
authors.lastname: Mozingo
mesh_terms: D000818:Animals; D017209:Apoptosis; D002056:Burns / Q000276:immunology* / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D004792:Enzyme Precursors / Q000096:biosynthesis*; D053222:Fas Ligand Protein; D005260:Female; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D004792:Enzyme Precursors; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases