title: Hypercapnic acidosis prolongs survival of skin allografts.
abstract: BACKGROUND
  Evidence reveals that hypercapnic acidosis (HCA) modulates immune responses. However, the effect of HCA on allogenic skin graft rejection is unknown. We examined whether HCA might improve skin graft survival in a mouse model of skin transplantation.
  
  
  METHODS
  A major histocompatibility-complex-incompatible BALB/c to C57BL/6 mouse skin transplantation model was used. Animals were divided into sham control, air, and HCA groups. Mice in the HCA group were exposed daily to 5% CO2 in air for 1 h. Skin grafts were harvested for histologic analyses. Nuclear factor (NF)-κB activation was determined in harvested draining lymph nodes. Spleen weights and serum levels of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 2 were serially assessed after skin transplantation.
  
  
  RESULTS
  Skin allografts survived significantly longer in the HCA group of mice than those in the air group. Allografted mice in the air group underwent a 2.1-fold increase in spleen weight compared with a 1.1-fold increase in the mice with HCA on day 3. There were increased inflammatory cell infiltration, folliculitis, focal dermal-epidermal separation, and areas of epidermal necrosis in the air group that were reduced with HCA treatment. In the HCA group, CD8(+) T cell infiltration at day 7 decreased significantly but not CD4(+) T cell infiltration. In addition, HCA significantly suppressed serum tumor necrosis factor-α on days 1 and 3 and chemokine (C-X-C motif) ligand 2 on days 1 and 10. Furthermore, the HCA group had remarkably suppressed NF-κB activity in draining lymph nodes.
  
  
  CONCLUSIONS
  HCA significantly prolonged the survival of incompatible skin allografts in mice by reducing proinflammatory cytokine production, immune cell infiltration, and NF-κB activation.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yuan-Sheng
authors.initials: YS
authors.lastname: Tzeng
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Peng
authors.affiliation: Department and Graduate institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chia-Pi
authors.initials: CP
authors.lastname: Cheng
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-En
authors.initials: SE
authors.lastname: Tang
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: d1204812@mail.ndmctsgh.edu.tw.
authors.forename: Shi-Jye
authors.initials: SJ
authors.lastname: Chu
mesh_terms: D064591:Allografts / Q000473:pathology / Q000502:physiology*; D000818:Animals; D054426:Chemokine CXCL2 / Q000097:blood; D006085:Graft Survival; D006935:Hypercapnia; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D012867:Skin / Q000473:pathology; D016038:Skin Transplantation; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: Hypercapnic acidosis; Nuclear factor-κB; Skin allograft; Transplantation; Tumor necrosis factor-α