title: E-Selectin Mediates Immune Cell Trafficking in Corneal Transplantation.
abstract: BACKGROUND
  Immune rejection continues to threaten all tissue transplants. Here we sought to determine whether platelet (P)- and endothelial (E)-selectin mediate T cell recruitment in corneal transplantation and whether their blockade can reduce T cell graft infiltration and improve long-term corneal allograft survival.
  
  
  METHODS
  In a murine model of allogeneic corneal transplantation, we used PCR and immunohistochemistry to investigate expression of P- and E-selectin in rejected versus accepted allografts and lymph node flow cytometry to assess expression of selectin ligands by effector T cells. Using P- and E-selectin neutralizing antibodies, we evaluated the effect of blockade on CD4 T cell recruitment, as well as the effect of anti-E-selectin on long-term allograft survival.
  
  
  RESULTS
  The P- (93.3-fold, P < 0.05) and E-selectin (17.1-fold, P < 0.005) are upregulated in rejected versus accepted allogeneic transplants. Type 1 T helper cells from hosts with accepted and rejected grafts express high levels of P-selectin glycoprotein ligand 1 and glycosylated CD43. In vivo blockade of P (0.47 ± 0.03, P < 0.05) and E selectin (0.49 ± 0.1, P < 0.05) reduced the number of recruited T cells compared with IgG control (0.98 ± 0.1). Anti-E-selectin reduced the number of mature antigen-presenting cells trafficking to lymphoid tissue compared with control (6.96 ± 0.9 vs 12.67 ± 0.5, P < 0.05). Anti-E-selectin treatment delayed graft rejection and increased survival compared with control, although this difference did not reach statistical significance.
  
  
  CONCLUSIONS
  In a model of corneal transplantation, P- and E-selectin mediate T cell recruitment to the graft, E-selectin mediates APC trafficking to lymphoid tissue, and blockade of E-selectin has a modest effect on improving long-term graft survival.
authors.affiliation: 1 Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA. 2 Cornea Service, New England Eye Center/Tufts Medical Center, Department of Ophthalmology, Tufts University School of Medicine, Boston, MA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Dohlman
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Zazzo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Omoto
authors.forename: Jing
authors.initials: J
authors.lastname: Hua
authors.forename: Julia
authors.initials: J
authors.lastname: Ding
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D016039:Corneal Transplantation; D019040:E-Selectin / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D057134:Antibodies, Neutralizing; D019040:E-Selectin; D007166:Immunosuppressive Agents; D008024:Ligands; D019007:P-Selectin