Purchase this article with an account.
Thomas H Dohlman, Sunil K Chauhan, Masahiro Omoto, Jing Hua, Zahra Sadrai, Pedram Hamrah, Reza Dana; Expression of P- and E-Selectin in Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3220.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Corneal allograft rejection is predominantly mediated by T lymphocytes, which must exit the vasculature in order to infiltrate the graft. The purpose of this study was to determine the expression of P- and E- selectin, adhesion molecules involved in immune cell recruitment, in a murine model of corneal transplantation.
Donor corneal buttons from 6-8 week old male C57BL/6 mice were sutured onto age and sex matched BALB/c host mice and followed for graft opacity. Four weeks following transplantation, accepted and rejected grafts were collected and evaluated for gene and protein expression of P- and E- selectin by real-time PCR and corneal whole-mount immunohistochemistry. In addition, T helper (Th) 1 cells from the ipsilateral submandibular and cervical lymph nodes of graft acceptors and rejectors were evaluated for expression of the selectin ligands PSGL-1 and GlycoCD43 using flow cytometry.
Compared to acceptors, the graft and host bed of rejectors demonstrated a 90-fold increase in P-selectin mRNA (p<0.05) and a 17-fold increase in E-selectin mRNA expression (p<0.005). Immunohistochemical staining confirmed a significant increase in P- and E-selectin expression in rejected grafts, and showed that these receptors co-localize with CD31+ vascular endothelial vessels. Using flow cytometry, we found that in both acceptors and rejectors, approximately 90% of CD4+IFN-γ+ Th1 cells express PSGL-1 and GlycoCD43. The level of PSGL-1 expression by Th1 cells increased significantly in rejected mice as compared to acceptors (MFI: 184 vs.152, p=0.01), while no difference in GlycoCD43 expression between acceptors and rejectors was observed (MFI: 131 vs.125).
In rejected corneal transplants, there is an increase in expression of P- and E- selectin by vascular endothelial cells, as well as an increase in PSGL-1 expression by Th1 cells in draining lymph nodes. These findings suggest that selectins are important in Th1 cell recruitment, and that disruption of selectin binding may represent a strategy for preventing Th1 cell infiltration of transplants, thus promoting allograft survival.
This PDF is available to Subscribers Only