Background: Mast cells (MC) are resident in healthy hearts and play important physiological and pathophysiological roles. In the transplanted heart, correlations have been found between MC number and the severity of rejection episodes, the intensity of chronic inflammation, and allograft arteriosclerotic changes. However, not much emphasis has been placed on the fact that resident donor MC, and infiltrating recipient MC do not forcedly need to share the same properties and function. To gain insight in the role of cardiac MC during acute, and ongoing acute rejection of heart transplants, we investigated MC kinetics and MC phenotype in a rat heart transplantation model.
Methods: Donor hearts from female Brown-Norway rats were transplanted to male Lewis rats. Immunosuppression was started at day 5 using ciclosporin and prednisolone. Connective tissue type MC (CTMC) were distinguished from mucosa type MC (MMC) by immunohistochemistry for rat MC protease (RMCP) -1 and -2. Expression of RMCP-1 and -2 mRNA was quantified by real time reverse transcription-polymerase chain reaction. Infiltrating Y chromosome positive MC were detected by fluorescence in situ hybridization. mRNA expression of interleukin-3 (IL-3) and of the two differentially spliced isoforms of kit ligand (KL, stem cell factor) was quantified using reverse transcription-polymerase chain reaction.
Results: Resident cardiac donor MC are almost exclusively CTMC and decrease in number during acute rejection. MC increase in number, and recipient MC invade the cardiac allograft during ongoing acute rejection. The phenotype of the invading MC is characterized by the expression of RMCP-2, or both RMCP-1 and RMCP-2, and thus resemble a MMC type. IL-3 mRNA is highly expressed, and the ratio of the differentially spliced mRNAs for KL-1 and KL-2 rises up to 2-fold during ongoing acute rejection.
Conclusions: Our data show that MC in posttransplant hearts during ongoing acute rejection differ from MC in healthy hearts and isografts by expressing a different phenotype. Changes in IL-3 and KL expression might be responsible for the predominance of MMC over CTMC. The notion is of importance that MC in cardiac allografts may have properties and functions that differ from those in nontransplanted healthy hearts.