Platelet-endothelial cell adhesion molecule-1 (CD31) expression on donor endothelial cells attenuates the development of transplant arteriosclerosis

Abstract

Background. Platelet-endothelial cell adhesion molecule(PECAM)-1 (CD31) is expressed on the surface of endothelial cells, platelets, monocytes, neutrophils, and certain T-cell subsets. Treatment of endothelial cells with anti-PECAM-1 antibody inhibits leukocyte transmigration. This study was designed to test the hypothesis that, in transplantation, the absence of PE-CAM-1 expression on donor endothelial cells would reduce the number of leukocytes transmigrating into the allograft, thereby attenuating the development of transplant arteriosclerosis. Methods. PECAM-1-/- and PECAM+/+ (C57BL/6/H2b) abdominal aortic allografts were transplanted into BALB/c (H2d) recipients; syngeneic grafts were used as controls. Aortic grafts were analyzed by performing morphometry, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction for the detection of intragraft cytokine mRNA production. Results. Intimal proliferation was exacerbated in PECAM-1-/- grafts (57±5% for PECAM-1-/- vs. 36±6% for PECAM-1+/+; P<0.005; n=6). The absence of PE-CAM-1 expression on donor endothelial cells did not reduce the overall number of graft-infiltrating cells significantly but instead resulted in a significant increase in infiltration by macrophages (F4/80+ cells), leading to significantly elevated intragraft mRNA expression of inducible nitric oxide synthase. During the development of transplant arteriosclerosis, PECAM-1-/- donor endothelial cells were replaced by recipient PECAM-1+/+ endothelial cells, a process that occurred only in the allogeneic situation. Endothelial replacement commenced 14 days after transplantation and was complete by day 30. Conclusions. These data suggest that PECAM-1 expression by donor endothelial cells attenuates the development of transplant arteriosclerosis, possibly by affecting macrophage infiltration.