Analysis of macrophage phenotype in rejected corneal allografts.
PURPOSE
We investigated the phenotype of macrophages infiltrating rejected corneal allografts.


METHODS
We performed allogeneic or syngeneic corneal transplantation in mice, and humanely killed animals at day 28 during allograft rejection when 60% of corneal allografts were rejected. We divided allografts into two groups: grafts with rejection as rejectors and grafts without rejection as nonrejectors, and analyzed for macrophage infiltration and their phenotype using immunohistochemistry. In addition, we investigated the time course of proinflammatory cytokines and chemokines by analyzing corneal grafts at days 7, 28, and 42 using real-time RT-PCR. Also, we assayed human corneal allografts with chronic graft failure.


RESULTS
We found that a large number of CD11b(+), F4/80(+), or inducible nitrous oxide synthase cells (iNOS(+)) infiltrated corneal allografts during rejection in mice, while the cells were found rarely in syngeneic or allogeneic grafts that were not rejected. There were rare CD11c(+) cells in rejectors and nonrejectors. Many mannose receptor cells (MRC(+)) were present in nonrejectors, but not in rejectors. The levels of Th1 cytokines, IFN-γ, and IL-2 were highly increased in rejectors at day 28, indicating immune rejection. Also, the levels of IL-12a, IL-1β, TNF-α, CCL3, and iNOS that are produced by activated macrophages were markedly increased in rejectors at day 28, compared to syngeneic grafts or nonrejectors. Similarly, human corneal allografts with chronic graft failure had higher levels of IL-12a, IL-1β, CCL3, and iNOS than controls.


CONCLUSIONS
Increased numbers of macrophages in rejected corneal allografts implicate that these cells might contribute to the immunopathogenesis of corneal graft rejection.
['Oh|Joo Youn|JY|', 'Lee|Hyun Ju|HJ|', 'Ko|Ah Young|AY|', 'Ko|Jung Hwa|JH|', 'Kim|Mee Kum|MK|', 'Wee|Won Ryang|WR|']
D064591:Allografts D000818:Animals D018925:Chemokines D003315:Cornea D003316:Corneal Diseases D016039:Corneal Transplantation D004247:DNA D004195:Disease Models, Animal D005260:Female D005500:Follow-Up Studies D005786:Gene Expression Regulation D006084:Graft Rejection D006085:Graft Survival D006801:Humans D007150:Immunohistochemistry D008264:Macrophages D051379:Mice D008810:Mice, Inbred C57BL D008875:Middle Aged D010641:Phenotype D060888:Real-Time Polymerase Chain Reaction
macrophages rejection corneal transplantation