Macrophages Fascilate Chronic Cardiac Rejection through a Monocyte-Induced by IFNγ (MIG) Mediated Process (145.14)

Abstract Introduction Chronic rejection (CR) in cardiac transplantation leads to allograft dysfunction and transplant related heart failure. We investigated the role of macrophages-associated chemokines, monocyte-induced by IFNγ (MIG) and IFN-inducible protein 10 (IP-10) and their receptor CXCR3, in chronic cardiac allograft rejection. Methods BALB/c (H-2d) hearts were transplanted into C57BL6 (H-2b) recipients (n=6). Group AR had no treatment. Group CR had 3 mg i.p. of GK1.5 (antiCD4). The hearts were analyzed using qRTPCR and IHC. The spleens underwent FACS analysis. CXCR3 transgenic(Tg) and CXCR3KO mice were transplanted with BALB/c hearts. Results In group AR, hearts rejected at day 7. In group CR, the functioning hearts were harvested at day 30. Using ICH group CR allografts had significantly more macrophages compared to both AR allografts and isografts. FACS analysis of splenocytes in group CR detected macrophages to be more abdundant compared to group AR (p<0.05). qRTPCR analysis detected a significant increase in allograft MIG and IP-10 in the group AR,(p<0.05)but only MIG was significantly upregulated in group CR relative to both group AR and isografts(p<0.05). CXCR3Tg and CXCR3KO transplants rejected at day 7. Conclusions Chronic cardiac allograft rejection may be a macrophage dependent process, potentially mediated through MIG. However, our results suggest that MIG and its receptor are likely to only be one component of a highly complicated process.