Title: Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8
Authors: Fan, Xuedong ×
Patera, Andriani C
Pong-Kennedy, Amy
Deno, Gregory
Gonsiorek, Waldemar
Manfra, Denise J
Vassileva, Galya
Zeng, Ming
Jackson, Craig
Sullivan, Lee
Sharif-Rodriguez, Wanda
Opdenakker, Ghislain
Van Damme, Jozef
Hedrick, Joseph A
Lundell, Daniel
Lira, Sergio A
Hipkin, R. William #
Issue Date: Apr-2007
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:282 issue:16 pages:11658-11666
Abstract: Functional interleuin-8 ( IL-8) receptors ( IL-8RA and IL-8RB: CXCR1 and CXCR2, respectively) have been described in human, monkey, dog, rabbit, and guinea pig. Although three IL-8R homologues have been found in rat, only one of these, rat CXCR2, appears to be functional based on responsiveness to ligands. Similarly, CXC chemokines induce biological responses through the murine homolog of CXCR2, but the identification of functional rodent CXCR1 homologues has remained elusive. We have identified and characterized the mouse CXCR1 homologue ( mCXCR1). Murine CXCR1 shares 68 and 88% amino acid identity with its human and rat counterparts, respectively. Similar to the tissue distribution pattern of rat CXCR1, we found murine CXCR1 mRNA expression predominantly in lung, stomach, bone marrow, and leukocyte-rich tissues. In contrast to previous reports, we determined that mCXCR1 is a functional receptor. We show predominant engagement of this receptor by mouse GCP-2/CXCL6, human GCP-2, and IL-8/CXCL8 by binding, stimulation of GTP gamma S exchange, and chemotaxis of mCXCR1-transfected cells. Furthermore, murine CXCR1 is not responsive to the human CXCR2 ligands ENA-78/CXCL5, NAP-2/CXCL7, GRO-alpha, -beta, -gamma/CXCL1-3, or rat CINC-1-3. In addition, we show concomitant elevation of mCXCR1 and its proposed major ligand, GCP-2, positively correlated with paw swelling in murine collagen-induced arthritis. This report represents the first description of a functional CXCR1-like receptor in rodents.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
Laboratory of Molecular Immunology (Rega Institute)
× corresponding author
# (joint) last author

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