Pneumologie 2004; 58 - V289
DOI: 10.1055/s-2004-819647

Recipient-specific Immunosuppression by Donor-derived Suppressor Macrophages in porcine Lung Transplantation

M Strueber 1, G Warnecke 1, F Fändrich 2, SP Sommer 1, T Steinkamp 1, M Avsar 1, C Peters 1, R Reinhard 1, G Zehle 2, M Ruhnke 2, S Fischer 1, AR Simon 1, J Niedermeyer 3, A Haverich 1
  • 1Medizinische Hochschule Hannover, Thorax-, Herz- und Gefäßchirurgie, Hannover
  • 2Universität Kiel, Allgemein und Thoraxchirurgie, Kiel
  • 3Medizinische Hochschule Hannover, Pneumologie, Hannover

Background: Isolated and M-CSF-stimulated donor macrophages induced indefinite rat heart allograft survival. This approach is to be evaluated in porcine lung transplantation.

Methods: Lung transplantation from MHC mismatched donors was performed in 18 minipigs. Animals received 1–10×106 isolated, cultured (6 days) and M-CSF stimulated donor macrophages on POD0 (n=1), POD7 (n=5) or POD7 after 7Gy preoperative thymic and 1,5Gy whole body irradiation (n=6). Six animals served as controls. Immunosuppression included 1.5mg/kg/d methylprednisolone and 1.0mg/kg/d azathioprine. FK 506 was adjusted to 16–26 ng/ml. Immunosuppressive drugs were discontinued on POD 28. Allograft survival was monitored by chest x-rays, bronchoscopy and transbronchial biopsy histology.

Results: All animals survived the 28 day course of immunosuppression without signs of rejection. Control animals survived 147±59 days with one animal currently alive at POD 350. Macrophages on POD0 resulted in longterm allograft acceptance (POD610) and on POD7 in mean survival of 123±38 days with one animal currently alive at POD481. Combined treatment with macrophages and preoperative irradiation resulted in longterm allograft survival in 3 out of 6 animals.

Conclusions: The cotransplantation of macrophages at the time of transplantation leads to chronic allograft survival, but macrophages on POD7 do not prevent rejection. Macrophage treatment on POD7 is more efficient after preoperative thymic irradiation.