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

Abstract

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.

Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

“…The abundance of CXCL9 in urine [24] and that of soluble CD44 in plasma [25] have previously been shown to increase in renal AR compared with STA. In addition, macrophage surface PECAM1 can distinguish lung transplant rejection [41] but is not diagnostic in mouse models of cardiac transplant rejection [42]. But to our knowledge, this study is the first to show all three markers as cross-organ AR protein biomarkers in human serum or plasma.…”

Erythropoietin inhibits post-ischemic leukocyte adhesion but does not affect rejection in murine cardiac allografts

“…It has to be noted that the transplantation model used herein, BALB-c to C57BL/6, provokes relatively vigorous acute rejection within approximately 1 week. 44 The anti-inflammatory effect of Epo may have been simply overshadowed by fulminant acute rejection, which could not have even been blunted by cyclosporine. It remains to be determined whether escalation of adjunctive immunosuppression or use of a weaker rejection model may uncover long-lasting Epodriven protection in cardiac transplantation.…”

Progenitor Cell Homing in the Postischemic Myocardium: Just an Unmotivated Pitstop in the Microcirculation?

“…In the following text, these animals are referred to as atherosclerotic ApoE −/− mice. In addition, we used age‐matched C57BL/6, PECAM molecule‐1‐deficient (CD31 −/− ) and LFA‐1‐deficient (CD11a −/− ) mice, which were fed standard pellet food (Altromin, Lage, Germany; ). All experiments were performed in accordance with the legislation on the protection of animals and were approved by the Governmental Ethical Committee for Animal Experimentation.…”