title: Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8.
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 GTPgammaS 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.
authors.affiliation: Inflammation Department, Discovery Technologies Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Fan
authors.forename: Andriani C
authors.initials: AC
authors.lastname: Patera
authors.forename: Amy
authors.initials: A
authors.lastname: Pong-Kennedy
authors.forename: Gregory
authors.initials: G
authors.lastname: Deno
authors.forename: Waldemar
authors.initials: W
authors.lastname: Gonsiorek
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Manfra
authors.forename: Galya
authors.initials: G
authors.lastname: Vassileva
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Craig
authors.initials: C
authors.lastname: Jackson
authors.forename: Lee
authors.initials: L
authors.lastname: Sullivan
authors.forename: Wanda
authors.initials: W
authors.lastname: Sharif-Rodriguez
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hedrick
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundell
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.forename: R William
authors.initials: RW
authors.lastname: Hipkin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000378:metabolism*; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D023062:Receptors, Interleukin-8A / Q000235:genetics* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
chemical_list: C515503:CXCL6 protein, human; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D003094:Collagen