Yuan-Sheng Tzeng1, Shu-Yu Wu2, Yi-Jen Peng3, Chia-Pi Cheng4, Shih-En Tang2, Kun-Lun Huang2, Shi-Jye Chu5. 1. Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 2. Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. 3. Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 4. Department and Graduate institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. 5. 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.
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.
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: Ciara E Keogh; Carsten C Scholz; Javier Rodriguez; Andrew C Selfridge; Alexander von Kriegsheim; Eoin P Cummins Journal: J Biol Chem Date: 2017-05-15 Impact factor: 5.157
Authors: Avinoam Nevler; Samantha Z Brown; David Nauheim; Carla Portocarrero; Ulrich Rodeck; Jonathan Bassig; Christopher W Schultz; Grace A McCarthy; Harish Lavu; Theresa P Yeo; Charles J Yeo; Jonathan R Brody Journal: J Am Coll Surg Date: 2020-02-11 Impact factor: 6.113