Title: AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor-deficient mice
Authors: Matthys, Patrick ×
Hatse, Sigrid
Vermeire, Kurt
Wuyts, Anja
Bridger, G
Henson, G W
De Clercq, Erik
Billiau, Alfons
Schols, Dominique #
Issue Date: Oct-2001
Publisher: American Association of Immunologists
Series Title: Journal of Immunology vol:167 issue:8 pages:4686-4692
Abstract: Autoimmune collagen-induced arthritis (CIA) in IFN-gammaR-deficient DBA/1 mice was shown to be reduced in severity by treatment with the bicyclam derivative AMD3100, a specific antagonist of the interaction between the chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4. The beneficial effect of the CXCR4 antagonist was demonstrable when treatment was initiated between the time of immunization and appearance of the first symptoms. Treatment also reduced the delayed-type hypersensitivity response to the autoantigen, collagen type II. These observations are indicative of an action on a late event in the pathogenesis, such as chemokine-mediated attraction of leukocytes toward joint tissues. The notion of SDF-1 involvement was further supported by the observation that exogenous SDF-1 injected in periarthritic tissue elicited an inflammatory response that could be inhibited by AMD3100. The majority of leukocytes harvested from inflamed joints of mice with CIA were found to be Mac-1(+) and CXCR4(+), and AMD3100 was demonstrated to interfere specifically with chemotaxis and Ca(2+) mobilization induced in vitro by SDF-1 on Mac-1(+)/CXCR4(+) splenocytes. We conclude that SDF-1 plays a central role in the pathogenesis of murine CIA, by attracting Mac-1(+)/CXCR4(+) cells to the inflamed joints.
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Laboratory of Immunobiology (Rega Institute)
Laboratory of Experimental Oncology
Laboratory of Molecular Immunology (Rega Institute)
× corresponding author
# (joint) last author

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