Prevention of crescentic glomerulonephritis by immunoneutralization of the fractalkine receptor CX3CR1 rapid communication.
BACKGROUND
Fractalkine is a newly identified T-cell and monocyte/macrophage (Mphi) chemokine with a transmembrane domain and is a cell-surface protein on activated endothelium. It can mediate adhesion of cells expressing the fractalkine receptor CX3CR1. 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 CX3CR1. Anti-CX3CR1 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 CX3CR1 as a prime drug target for therapeutic intervention of endothelium-related inflammatory diseases.
Feng
L
L
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. llfimm@scripps.edu
Chen
S
S
Garcia
G E
GE
Xia
Y
Y
Siani
M A
MA
Botti
P
P
Wilson
C B
CB
Harrison
J K
JK
Bacon
K B
KB
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001485:Basement Membrane / Q000737:chemistry / Q000276:immunology; D001798:Blood Proteins / Q000494:pharmacology; D000073883:CX3C Chemokine Receptor 1; D002633:Chemotaxis / Q000276:immunology; D004727:Endothelium / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D005921:Glomerulonephritis / Q000276:immunology* / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY; D018121:Receptors, Cytokine / Q000276:immunology*; D015728:Receptors, HIV / Q000276:immunology*
D000906:Antibodies; D001798:Blood Proteins; D000073883:CX3C Chemokine Receptor 1; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV