The Implication of Monocyte/Macrophage into the Graft Following Heart Transplantation in Rat

ABSTRACT

BACKGROUND: In organ transplantation, the cellular immune reaction, namely T-cell immunity, plays a major role in rejecting the graft. While T & B cell activities in organ transplantation have been studied extensively, monocytes/macrophages have not because of their a minor role in innate immunity. Monocytes act as immunologically active cells in several aspects in organ transplantation, such as antigen-presenting cells, cells releasing many substance, such as IL-1, IL-2, TNF-alpha, and many growth factors, and cells phagocytosing foreign antigens and tissues in the effector phase of immune reaction. METHODS: We attempted to study the role of monocytes/ macrophages in graft rejection following allogenic organ transplantation in rodents. RESULTS: While graft survivals following a cardiac allograft were more then 100 days in all the singenic Wistar to Wistar transplants, the graft survival for Lewis to Wistar allografts were 7 to 12 days with a mean of 9.2 days. In the histology of the transplanted hearts, cellular infiltration developed from posttransplantation day 1, and all the histologic findings, such as myocardial ischemia, interstitial bleeding, and endocardial changes, were more progressive around the days of graft rejection. Macrophage infiltration analyzed by immunohistochemstry using the spectific antibody ED1, was noticed from postoperative day 1, and the macrophages were distributed all through the layer of the heart. In the study on the intragraft monokine gene by using RT-PCR, mRNA of IL-1 expressed on day 1 and reappearedon day 7. mRNA of TNF-alphaexpressed on day 3 and MCP-1 on day 1. All the monokine gene expressions progressed up to the days of rejection. CONCLUSION: From these results showing the concurrent pattern of cell infiltration and intragraft cytokine gene expression of monocytes/macrophages with the lymphocyte, we suggest that intervention of monocytes in organ transplantation may prolong graft survival with or without the anti T cell strategy.