Session Name: Ischemia Reperfusion & Organ Rehabilitation
Session Date & Time: None. Available on demand.
*Purpose: We have previously demonstrated that donor genetic background and kidney-intrinsic innate immunity were key determinants of delayed graft function in kidney transplantation. However, the long-term effect and mechanism of ischemia/reperfusion injury (IRI) on graft rejection remains unclear.
*Methods: Kidneys from C57BL/6 (B6) or Balb/c mice were harvested and stored in cold UW solution for 3 hours, and then were transplanted into bi-nephrectomized C3H mice. Graft survival, renal function, pathological change of grafts, immunophenotypic analysis, and expression of involved genes, were determined. Renal tubular epithelial cells (RTECs) isolated from B6 or BALB/c mouse kidneys were stimulated by lipopolysaccharide (LPS) or Pam3CSK4, and cytokines and kidney injury molecule-1 (KIM-1) in supernatant were measured.
*Results: We found that when cold ischemia time was prolonged to 3 hours, rejection occurred earlier in kidney grafts from B6 mice compared with grafts from Balb/c mice. Correspondingly, recipients received B6 kidneys exhibited more severe impaired renal function, higher hematocrit level and more weight loss than recipients received Balb/c kidneys within 14 days post transplantation. Furthermore, B6 kidney grafts showed more severe histological impairment, increased Ly6C+CCR2+CX3CR1+/- inflammatory monocyte and CD8 memory T cell infiltration, accompanying by upregulation of IL-6 and endoplasmic reticulum stress genes. In vitro studies revealed that, in responding to either LPS (TLR4 agonist) or Pam3CSK4 (TLR1/TLR2 agonist) stimulation, RTECs from B6 mice produced lower level of cytokines including IL-6, IL-10, TNFα and MCP-1, but significantly higher level of the tubular cell injury marker KIM-1, in comparison with RTECs from Balb/c mice. Taken together, these results indicate that Balb/c kidneys were less vulnerable to IRI-induced rejection than B6 kidneys, which involves in activation of TLR depending innate immunity.
*Conclusions: We conclude that augmented responses of donor kidney tubular cells to TLR signaling plays a pivotal role in ameliorated ischemia/reperfusion injury and long-term allograft protection.
To cite this abstract in AMA style:Lai X, Wang J, Qiu L, Han S, Shen K, Zhang Z. Augmented Responses of Donor Kidney Tubular Cells to TLR Signaling Correlate with Ameliorated Ischemia/reperfusion Injury and Long-term Allograft Protection [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/augmented-responses-of-donor-kidney-tubular-cells-to-tlr-signaling-correlate-with-ameliorated-ischemia-reperfusion-injury-and-long-term-allograft-protection/. Accessed June 23, 2021.
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