A novel mechanism of anti-T-lymphocyte globulin mediated by fractalkine in renal ischemia-reperfusion injury in rats

Transplant Proc. 2013 Jul-Aug;45(6):2461-8. doi: 10.1016/j.transproceed.2013.02.118.

Abstract

Background: Ischemia-reperfusion injury (IRI) is among the main challenges in kidney transplantation. It causes delayed graft function and graft loss in long-term follow-up studies. Anti-T lymphocyte globulin (ATG), a common induction immunosuppressive, has been used in kidney transplantation to prevent rejection. Fractalkine (FKN) is among the main chemokines involved in IRI. This study was designed to identify the relationship between ATG and FKN after warm ischemia in rat kidneys.

Methods: Rats were divided into three groups: Control, IRI+normal saline(NS) and IRI+ATG. After IRI was initiated, rats received a dose of ATG or NS during surgery as well as two more doses at 24 and 48 hours after surgery. All rats were humanely killed at 72 hours.

Results: The concentration of FKN as well as dendritic cells (DC) and macrophages were lower in both peripheral blood and the injured kidney among ATG-treated versus control rats. Additionally cell necrosis, cytoplasmic vacuolization, cast formation, and tubular dilatation were improved among ATG-treated rats. Serum creatinine levels were lower in rats that received ATG.

Conclusion: ATG depleted the concentration of FKN, which inhibits migrations of DCs and macrophages into the kidney, and reduces IRI-related pathology.

MeSH terms

  • Animals
  • Antilymphocyte Serum / pharmacology*
  • Biomarkers / blood
  • Chemokine CX3CL1 / metabolism*
  • Chemotaxis / drug effects
  • Creatinine / blood
  • Cytoprotection
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Immunosuppressive Agents / pharmacology*
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Time Factors
  • Warm Ischemia / adverse effects*

Substances

  • Antilymphocyte Serum
  • Biomarkers
  • Chemokine CX3CL1
  • Cx3cl1 protein, rat
  • Immunosuppressive Agents
  • Creatinine