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.
Schramm
René
R
Department for Thoracic and Cardiovascular Surgery, University of Saarland, University Hospitals Homburg/Saar, Kirrbergerstrasse, D-66421 Homburg/Saar, Germany. reneschramm@hotmail.com
Menger
Michael D
MD
Schmits
Rudolf
R
Harder
Yves
Y
Kirsch
Sarah
S
Meier
Christoph
C
Schäfers
Hans-Joachim
HJ
D000818:Animals; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology* / Q000503:physiopathology; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*; D014184:Transplantation, Homologous
D000949:Histocompatibility Antigens Class II; D019408:Platelet Endothelial Cell Adhesion Molecule-1