Purpose: We sought to test the hypothesis that monocytes contribute to the immunopathogenesis of corneal allograft rejection and identify therapeutic targets to inhibit monocyte recruitment. Methods: Monocytes and proinflammatory mediators within anterior chamber samples during corneal graft rejection were quantified by flow cytometry and multiplex protein assays. Lipopolysaccharide or @entity379 stimulation of monocyte-derived macrophages (MDMs) was used to generate inflammatory conditioned media (CoM). Corneal endothelial viability was tested by nuclear counting, @entity495 , and @entity2667 staining. Chemokine and @entity436 expression in monocytes and MDMs was assessed in microarray transcriptomic data. The role of chemokine pathways in monocyte migration across microvascular endothelium was tested in vitro by chemokine depletion or @entity436 inhibitors. Results: Inflammatory monocytes were significantly enriched in anterior chamber samples within 1 week of the onset of symptoms of corneal graft rejection. The @entity709 inflammatory CoM was cytopathic to transformed @entity1 corneal endothelia. This effect was also evident in endothelium of excised @entity1 @entity267 and increased in the presence of monocytes. Gene expression microarrays identified monocyte chemokine receptors and cognate chemokines in @entity709 inflammatory responses, which were also enriched in anterior chamber samples. Depletion of selected chemokines in @entity709 inflammatory CoM had no effect on monocyte transmigration across an endothelial blood-eye barrier, but selective @entity436 inhibition reduced monocyte recruitment significantly. Conclusions: We propose a role for inflammatory monocytes in endothelial cytotoxicity in corneal graft rejection. Therefore, targeting monocyte recruitment offers a putative novel strategy to reduce donor endothelial cell injury in survival of @entity1 corneal allografts.

Identification of Therapeutic Targets of Inflammatory Monocyte Recruitment to Modulate the Allogeneic XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity267 :: ('MESH:D065306', 'Disease') :: ['cornea'] @entity495 :: ('2697', 'Gene') :: ['connexin 43'] @entity2667 :: ('MESH:D011419', 'Chemical') :: ['propidium iodide'] @entity709 :: ('MESH:D007645', 'Disease') :: ['MDM'] @entity379 :: ('3458', 'Gene') :: ['IFN-y'] @entity436 :: ('7852', 'Gene') :: ['chemokine receptor']
@entity267 :: (MESH:D065306,Disease) :: ['Injury to Donor Cornea']
