Early ocular chemokine gene expression and leukocyte infiltration after high-risk corneal transplantation.
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.
Yamagami
Satoru
S
Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA. syamagami-tky@umin.ac.jp
Hamrah
Pedram
P
Zhang
Qiang
Q
Liu
Ying
Y
Huq
Syed
S
Dana
M Reza
MR
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
D018925:Chemokines; D012333:RNA, Messenger