Platelet-endothelial cell adhesion molecule-1 (CD31) expression on donor endothelial cells attenuates the development of transplant arteriosclerosis.
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 PECAM-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/H2 ) abdominal aortic allografts were transplanted into BALB/c (H2 ) 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; <0.005; n=6). The absence of PECAM-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.
Ensminger
Stephan M
SM
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Spriewald
Bernd M
BM
Steger
Ulrich
U
Morris
Peter J
PJ
Mak
Tak W
TW
Wood
Kathryn J
KJ
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse