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.
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-1donor 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.
Authors: Kenneth Cheung; Liang Ma; Guosu Wang; David Coe; Riccardo Ferro; Marco Falasca; Christopher D Buckley; Claudio Mauro; Federica M Marelli-Berg Journal: Proc Natl Acad Sci U S A Date: 2015-09-21 Impact factor: 11.205
Authors: Gregor Warnecke; Gang Feng; Ryoichi Goto; Satish N Nadig; Ross Francis; Kathryn J Wood; Andrew Bushell Journal: Am J Pathol Date: 2010-05-14 Impact factor: 4.307
Authors: Liang Ma; Claudio Mauro; Georgina H Cornish; Jian-Guo Chai; David Coe; Hongmei Fu; Daniel Patton; Klaus Okkenhaug; Guido Franzoso; Julian Dyson; Sussan Nourshargh; Federica M Marelli-Berg Journal: Proc Natl Acad Sci U S A Date: 2010-10-26 Impact factor: 11.205