title: Early ocular chemokine gene expression and leukocyte infiltration after high-risk corneal transplantation.
abstract: OBJECTIVE
  To determine the differential gene expression of chemokine species and leukocyte infiltration of grafts in the early pre-rejection postoperative period after high-risk (HR) compared to normal-risk (NR) corneal transplantation.
  
  
  METHODS
  Fully mismatched and syngeneic corneal grafts were performed in NR (avascular) and HR (vascularized) recipient beds of BALB/c murine hosts. Gene expression levels of a panel of chemokines were determined by a multiprobe ribonuclease protection assay system. The profiles of infiltrating cells into the corneal grafts at the same times were determined immunohistochemically.
  
  
  RESULTS
  Compared to NR transplantation, HR eyes exhibited significantly higher mRNA levels for macrophage inflammatory protein (MIP)-2 and monocyte chemotactic protein-1 (MCP-1) on day 1, and for eotaxin on days 1 and 3 after transplantation. By day 6 after transplantation, still well before graft rejection, significantly higher levels of RANTES, eotaxin, MIP-1alpha, MIP-1beta, MIP-2, and MCP-1 were detected in HR eyes. The overexpression of MIPs in HR eyes correlated with a significant increase in the number of infiltrating macrophages (p<0.01), and neutrophils (p<0.05) in HR compared to NR recipients. Low levels of eosinophil and mast cell infiltration were observed in all grafts, with a modest increase in mast cell infiltration (p<0.05) in HR compared to NR grafts.
  
  
  CONCLUSIONS
  These results suggest that increased expression of gene products for select chemokines, in particular those that mediate recruitment of innate immune cells, in the early period after HR corneal transplantation is related to the enhanced leukocytic infiltration of grafts observed in HR keratoplasty.
authors.affiliation: Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA. syamagami-tky@umin.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagami
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Syed
authors.initials: S
authors.lastname: Huq
authors.forename: M Reza
authors.initials: MR
authors.lastname: Dana
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D016510:Corneal Neovascularization / Q000378:metabolism / Q000601:surgery*; D016039:Corneal Transplantation; D005786:Gene Expression Regulation / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D014185:Transplantation, Isogeneic
chemical_list: D018925:Chemokines; D012333:RNA, Messenger