Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

Pre-programmed macrophages modify injury in immunocompetent mice with Adriamycin nephropathy

  • Dr Ying Wang, Centre for Transplantation and Renal Research, The University of Sydney at Westmead, Australia
  • Dr Yiping Wang, The University of Sydney at Westmead Millenium Institute, Australia
  • Guoping Zheng, Australia
  • Dr Vincent Lee, The University of Sydney at Westmead Millenium Institute, Australia
  • Deepika Mahajan, The University of Sydney at Westmead Millenium Institute, Australia
  • Prof David Harris, The University of Sydney at Westmead Millenium Institute, Australia

    • Introduction: Our previous studies demonstrated the marked potency of macrophages pre-programmed ex-vivo in manipulating renal injury in SCID (immunodeficient, no functioning T or B cells) mice with adriamycin nephropathy (AN). Here we investigated whether pre-programmed macrophages were also effective in exerting an effect on renal injury in immunocompetent (BALB/c) mice.
    Methods: AN was produced in male 6-8 weeks old mice by a single dose of Adriamycin (ADR 9.65mg/kg iv). Macrophages separated from normal mice (M0) were pre-programmed ex vivo by LPS (M1) or IL-4 and IL-13 (M2) to produce effector or regulatory phenotypes respectively. One million cells were transferred into treated mice by iv injection at day 5 after ADR. Six mice in each of groups A (ADR+saline treated), B (ADR + M0 macrophages), C (ADR + M1 macrophages) and D (ADR + M2 macrophages) were sacrificed and renal function and histopathological features were assessed on day 28.
    Results: Adoptive transfer of M0 macrophages to AN mice had no effect on proteinuria and tubular height compared with the mice given ADR+saline. However, transfer of M1 macrophages worsened whilst M2 macrophages ameliorated renal injury (A vs B vs C vs D: proteinuria 17.02±4.48 vs 17.83±4.06 vs 37.5±5.32 vs 8.3±1.79 mg/L, tubular height 8.17±1.64 vs 8.37±1.81 vs 4.80±0.94 vs 14.07±0.32 μm).
    Conclusion: These findings demonstrate that modulating ex vivo the phenotype of macrophages directly affects the capacity of these cells to modify renal injury in immunocompetent AN mice. Such macrophages can modify renal injury in the presence or absence of lymphocytes.

    Conference Organiser - ICMS Pty Ltd