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The role of Neutrophil Extracellular Traps (NETs) in skin allograft rejection
Arrin Brooks MD, Ph.D., Mihail Climov, MD, Luis Quiroga MD, Vlad Codrea MD, Ph.D., Emily Henderson MS, Brian Boone MD, Kerri Woodberry MD
West Virginia University
2023-02-10
Presenter: Arrin Brooks
Affidavit:
I certify this material has not been published or previously presented. This work represents the original work of the resident.
Director Name: Kerri Woodberry
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Wounds secondary to burns, trauma, or oncologic resection often require skin grafting. While autologous skin grafts are generally preferred for defect coverage, donor availability may be limited. When autograft supply is inadequate, skin allografts serve as alternatives. Given the highly immunogenic nature of skin, repeat application of cutaneous allografts is often necessary, with subsequent associated risks. Many current immunosuppressive medications are focused on the adaptive immune response. We sought to evaluate the role of neutrophil extracellular traps (NETs), which play a role in transplant rejection through the innate immune response. We investigated the potential effect of modulating the neutrophil response using an agent known to block neutrophil function, hydroxychloroquine (HCQ), on gross or histological rejection of skin allografts in mice. The study consisted of an HCQ-treated and control group, (n=8 per group) that were evaluated with daily photos. Histology was collected on days 4, 6, 8, and 12. NET cDNA was evaluated on days 6,8, and 12 in serum samples. We found no statistical difference between the allografted mice receiving HCQ vs control in planimetry analysis of graft rejection. Although non-significant, there was a trend towards improved survival in HCQ-treated mice. Although we noted double the NET cDNA in control vs. HCQ-treated mice on POD 8, there was no significant difference between serum NET levels at post-op day 6, 8, or 12. These data were underpowered to reveal statistical significance but demonstrate important pilot data for future studies to further elucidate HCQ's role in preventing or delaying cutaneous allograft rejection.
