New insight into mechanisms of allograft transplantation in the rat by differential display: Macrophage scavenger receptor-A brings to light

Background: Donor specific tolerance to heart allografts is induced in LEW. 1A rat recipient by two donor LEW.1W blood transfusions prior engraftment. Although the tolerant allograft is infiltrated by leukocytes, graft infiltr ating cells are only expressing low levels of the Th1- or Th2-related cytok ines suggesting that induction of tolerance is an active phenomenon in whic h the mechanisms remain to be elucidated. Materials and Methods: Differenti al display (DD) method was applied on RNAs extracted from graft infiltratin g cells (GIC) derived from allografts tither from rejecting untreated rats or donor-specific blood transfusion treated tolerant rats. Quantitative RT/ PCR was performed to confirm mRNA expressions of the selected genes. Results: Among the six differentially displayed DNAs (ddDNA) overexpressed in GIC from rejected allografts, the macrophage scavenger receptor-A (A:D13 265) was identified; it exhibited a stricking induction of mRNA expression from day 1 to 7 after transplantation. Among the seven ddDNAs overexpressed in GIC from tolerant allografts, the 3-hydroxy-3-methyl glutaryl coenzyme- A reductase (A:M29249) and an "unknown gene" (ddDNA EC9) were identified an d both were confirmed to be up-regulated by quantitative RT/PCR. Conclusions: The relevance of these genes in transplantation has not yet be en reported and must therefore be elucidated; they represent possible targe ts for immunointervention. Nevertheless, our data demonstrate that the DD i s a powerful tool to identify new genes involved in organ transplantation.