Thorac Cardiovasc Surg 2013; 61 - OP207
DOI: 10.1055/s-0032-1332446

Impact of Myeloperoxidase on tracheal graft rejection

M Stubbendorff 1, M Adam 1, 2, T Deuse 1, X Hua 3, S Baldus 1, H Reichenspurner 1, S Schrepfer 2, 3
  • 1Universitätsklinikum Hamburg Eppendorf, Universitäres Herzzentrum Hamburg, Hamburg, Germany
  • 2CT Surgery, Stanford University, Stanford, United States
  • 3Universitätsklinikum Hamburg Eppendorf, TSI Lab, Universitäres Herzzentrum Hamburg, Hamburg, Germany

Objectives: After solid organ transplantation, inflammatory mediators may contribute to the negative impacts on graft survival. Myeloperoxidase (MPO), a heme enzyme generously expressed by neutrophils, acts as a mediator of oxidative stress and is elevated in organ rejection. Suppression of nitrosative and oxidative stress reduces vasculopathy in cardiac allografts whereas neutrophil mediated smooth muscle cell loss promotes graft injury. Therefore we investigate the mechanistic involvement of MPO and its absence on trachea graft rejection.

Methods: Heterotopic trachea transplantations were performed in mice in allogeneic (CBA-to-C57BL/6), allogeneic knockout (CBA-to-C57BL/6 MPO-/-) and syngeneic (C57BL/6-to-C57BL/6) settings, and followed over 5 or 28 days. To study acute cellular rejection, unidirectional ELISPOT assays were performed after 5 days. For chronic rejection, tracheal luminal obliteration was quantified and Ly6G, marking neutrophiles, as well as leukocyte stainings were performed in the graft after 28 days.

Results: There was no significant difference in luminal obliteration of the MPO-/- versus the allogeneic transplantation. Also no significant differences could be observed in both, the neutrophile and total lymphocyte stainings. In unidirectional ELISPOT assays the MPO-/- group provoked a significantly stronger TH1 response (78 ± 56 vs. 33 ± 13 spots, p < 0.001) compared to the C57BL/6-to-C57BL/6 group.

Conclusions: Our results suggest, that the absence of MPO does not have a positive impact on trachea graft rejection. This may in part be a result of increased adaptive immunity through decreased neutrophil mediated CD4+-cell suppression in MPO deficient animals.