TI  - Molecular cloning of a novel human CC chemokine ( <prot>Eotaxin-3</prot> ) that is a
      functional ligand of  <prot>CC chemokine receptor 3</prot> .
PG  - 27975-80
AB  - Previously, we mapped the novel CC chemokine <prot>myeloid progenitor inhibitory
      factor 2</prot> (<prot>MPIF-2</prot>)/<prot>eotaxin-2</prot> to chromosome 7q11.23 (Nomiyama, H., Osborne,
      L. R., Imai, T., Kusuda, J., Miura, R., Tsui, L.-C., and Yoshie, O. (1998)
      Genomics 49, 339-340). Since chemokine genes tend to be clustered, unknown
      chemokines may be present in the vicinity of those mapped to new
      chromosomal loci. Prompted by this hypothesis, we analyzed the genomic
      region containing the gene for <prot>MPIF-2</prot>/<prot>eotaxin-2</prot> (<prot>SCYA24</prot>) and have
      identified a novel CC chemokine termed <prot>eotaxin-3</prot>. The genes for
      <prot>MPIF-2</prot>/<prot>eotaxin-2</prot> (<prot>SCYA24</prot>) and <prot>eotaxin-3</prot> (<prot>SCYA26</prot>) are localized within a
      region of approximately 40 kilobases. By Northern blot analysis, <prot>eotaxin-3</prot>
      mRNA was constitutively expressed in the heart and ovary. We have
      generated recombinant <prot>eotaxin-3</prot> in a baculovirus expression system.
      <prot>Eotaxin-3</prot> induced transient calcium mobilization specifically in <prot>CC
      chemokine receptor 3</prot> (<prot>CCR3</prot>)-expressing L1.2 cells with an EC(50) of 3 nM.
       <prot>Eotaxin-3</prot> competed the binding of (125) <prot>I-eotaxin</prot>  to  <prot>CCR3</prot>  -expressing L1.2
      cells with an IC(50) of 13 nM. <prot>Eotaxin-3</prot> was chemotactic for normal
      peripheral blood eosinophils and basophils at high concentrations.
      Collectively, <prot>eotaxin-3</prot>  is yet another functional ligand for  <prot>CCR3</prot> . The
      potency of <prot>eotaxin-3</prot> as a <prot>CCR3</prot> ligand seems, however, to be approximately
      10-fold less than that of <prot>eotaxin</prot>. Identification of <prot>eotaxin-3</prot> will
      further promote our understanding of the control of eosinophil trafficking
      and other <prot>CCR3</prot>-mediated biological phenomena. The strategy used in this
      study may also be applicable to identification of other unknown chemokine
      genes.
AD  - Shionogi Institute for Medical Science, Osaka 566-0022, Kinki University
