Prevention of crescentic glomerulonephritis by immunoneutralization of thefractalkine receptor CX(3)CR1 - Rapid communication

Background. Fractalkine is a newly identified T-cell and monocyte/macrophag e (M phi) chemokine with a transmembrane domain and is a cell-surface prote in on activated endothelium. It can mediate adhesion of cells expressing th e fractalkine receptor CX(3)CR1. These unique features make fractalkine wel l suited for leukocyte recruitment in tissues with high blood flow as in th e renal glomerulus. Methods. Fractalkine expression in glomeruli and response of isolated glome rular inflammatory cells to fractalkine were studied in the Wistar-Kyoto (W KY) crescentic glomerulonephritis model. Antibody was used to confirm the p roinflammatory role of fractalkine. Results. Fractalkine was markedly induced in the endothelium of nephritic r at glomeruli, and inflammatory leukocytes infiltrating the glomeruli expres sed increased levels of CX(3)CR1. Anti-CX(3)CR1 antibody treatment dramatic ally blocked leukocyte infiltration in the glomeruli, prevented crescent fo rmation, and improved renal function. Conclusions. Fractalkine plays a central role in leukocyte trafficking at t he endothelium in the high-flow glomerular circuit and, in turn, implicates CX(3)CR1 as a prime drug target for therapeutic intervention of endotheliu m-related inflammatory diseases.