Early ocular chemokine gene expression and leukocyte infiltrationafter high-risk corneal transplantation

摘要

Purpose: To determine the differential gene expression of chemokinespecies and leukocyte infiltration of grafts in the early pre-rejectionpostoperative period after high-risk (HR) compared to normal-risk (NR)corneal transplantation.Methods: Fully mismatched and syngeneic corneal grafts wereperformed in NR (avascular) and HR (vascularized) recipient beds ofBALB/c murine hosts. Gene expression levels of a panel of chemokineswere determined by a multiprobe ribonuclease protection assay system.The profiles of infiltrating cells into the corneal grafts at the sametimes were determined immunohistochemically.Results: Compared to NR transplantation, HR eyes exhibitedsignificantly higher mRNA levels for macrophage inflammatory protein(MIP)-2 and monocyte chemotactic protein-1 (MCP-1) on day 1, and foreotaxin on days 1 and 3 after transplantation. By day 6 aftertransplantation, still well before graft rejection, significantly higherlevels of RANTES, eotaxin, MIP-1α, MIP-1β, MIP-2, and MCP-1were detected in HR eyes. The overexpression of MIPs in HR eyescorrelated with a significant increase in the number of infiltratingmacrophages (p0.01), and neutrophils (p0.05) in HR compared toNR recipients. Low levels of eosinophil and mast cell infiltration wereobserved in all grafts, with a modest increase in mast cell infiltration(p0.05) in HR compared to NR grafts.Conclusions: These results suggest that increased expression of geneproducts for select chemokines, in particular those that mediaterecruitment of innate immune cells, in the early period after HR cornealtransplantation is related to the enhanced leukocytic infiltration ofgrafts observed in HR keratoplasty.