Role of PECAM-1 in Acute Rejection of Fully Major Histocompatibility Complex Class II-Mismatched Cardiac Allografts in Mice

The aim of this study was to determine the role of platelet-endothelial cell adhesion molecule (PECAM) in acute rejection of vascularized whole organ allografts in vivo. Hearts were transplanted between BALB/c, PECAM-1−/−, or C57BL/6 wild-type mice. Grafts were harvested on the day of rejection or after 120 days and were analyzed histologically. BALB/c allografts survived significantly longer in PECAM-1−/−recipients compared to wild-type controls (8.3±0.4 vs. 6.4±0.8 days; P<0.05). Survival of PECAM-1−/−allografts in BALB/c recipients did not differ from that of wild-type-derived transplants (12.2±3.0 vs. 9.3±0.7; P>0.05). In all allografts, histology showed massive monomorphonuclear leukocyte infiltration, indicating parenchymal rejection. Immunohistochemistry confirmed in all transplants a preserved donor endothelial phenotype. Our data indicate a subtle role of nonendothelial PECAM-1 in acute allograft rejection. Although deletion of PECAM-1 could not prevent rejection, it should be further evaluated as a therapeutic target in more complex settings with concomitant immunosuppression or during chronic rejection.