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- Title
Prevention of crescentic glomerulonephritis by immunoneutralization of the fractalkine receptor CX<sub>3</sub> CR1.
- Authors
Feng, Lili; Chen, Shizhong; Garcia, Gabriela E.; Xia, Yiyang; Siani, Mike A.; Botti, Paulo; Wilson, Curtis B.; Harrison, Jeffrey K.; Bacon, Kevin B.
- Abstract
Prevention of crescentic glomerulonephritis by immunoneutralization of the fractalkine receptor CX3 CR1. Background. Fractalkine is a newly identified T-cell and monocyte/macrophage (Mφ) chemokine with a transmembrane domain and is a cell-surface protein on activated endothelium. It can mediate adhesion of cells expressing the fractalkine receptor CX3 CR1. These unique features make fractalkine well suited for leukocyte recruitment in tissues with high blood flow as in the renal glomerulus. Methods. Fractalkine expression in glomeruli and response of isolated glomerular inflammatory cells to fractalkine were studied in the Wistar-Kyoto (WKY) crescentic glomerulonephritis model. Antibody was used to confirm the proinflammatory role of fractalkine. Results. Fractalkine was markedly induced in the endothelium of nephritic rat glomeruli, and inflammatory leukocytes infiltrating the glomeruli expressed increased levels of CX3 CR1. Anti-CX3 CR1 antibody treatment dramatically blocked leukocyte infiltration in the glomeruli, prevented crescent formation, and improved renal function. Conclusions. Fractalkine plays a central role in leukocyte trafficking at the endothelium in the high-flow glomerular circuit and, in turn, implicates CX3 CR1 as a prime drug target for therapeutic intervention of endothelium-related inflammatory diseases.
- Subjects
CHEMOKINES; IMMUNOGLOBULINS
- Publication
Kidney International, 1999, Vol 56, Issue 2, p612
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00604.x