PMID- 10488147 OWN - NLM STAT- MEDLINE DCOM- 19991104 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 39 DP - 1999 Sep 24 TI - Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3. PG - 27975-80 AB - Previously, we mapped the novel CC chemokine myeloid progenitor inhibitory factor 2 (MPIF-2)/eotaxin-2 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 MPIF-2/eotaxin-2 (SCYA24) and have identified a novel CC chemokine termed eotaxin-3. The genes for MPIF-2/eotaxin-2 (SCYA24) and eotaxin-3 (SCYA26) are localized within a region of approximately 40 kilobases. By Northern blot analysis, eotaxin-3 mRNA was constitutively expressed in the heart and ovary. We have generated recombinant eotaxin-3 in a baculovirus expression system. Eotaxin-3 induced transient calcium mobilization specifically in CC chemokine receptor 3 (CCR3)-expressing L1.2 cells with an EC(50) of 3 nM. Eotaxin-3 competed the binding of (125)I-eotaxin to CCR3-expressing L1.2 cells with an IC(50) of 13 nM. Eotaxin-3 was chemotactic for normal peripheral blood eosinophils and basophils at high concentrations. Collectively, eotaxin-3 is yet another functional ligand for CCR3. The potency of eotaxin-3 as a CCR3 ligand seems, however, to be approximately 10-fold less than that of eotaxin. Identification of eotaxin-3 will further promote our understanding of the control of eosinophil trafficking and other CCR3-mediated biological phenomena. The strategy used in this study may also be applicable to identification of other unknown chemokine genes. FAU - Kitaura, M AU - Kitaura M AD - Shionogi Institute for Medical Science, Osaka 566-0022, Kinki University School of Medicine, Osaka 589-8511, Japan. FAU - Suzuki, N AU - Suzuki N FAU - Imai, T AU - Imai T FAU - Takagi, S AU - Takagi S FAU - Suzuki, R AU - Suzuki R FAU - Nakajima, T AU - Nakajima T FAU - Hirai, K AU - Hirai K FAU - Nomiyama, H AU - Nomiyama H FAU - Yoshie, O AU - Yoshie O LA - eng SI - GENBANK/AB010447 PT - Journal Article PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CCL24 protein, human) RN - 0 (CCL26 protein, human) RN - 0 (CCR3 protein, human) RN - 0 (Ccl24 protein, mouse) RN - 0 (Ccr3 protein, mouse) RN - 0 (Chemokine CCL24) RN - 0 (Chemokine CCL26) RN - 0 (Chemokines, CC) RN - 0 (Chemotactic Factors) RN - 0 (Receptors, CCR3) RN - 0 (Receptors, Chemokine) RN - 0 (Recombinant Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cell Line MH - Chemokine CCL24 MH - Chemokine CCL26 MH - Chemokines, CC/*genetics/*metabolism MH - Chemotactic Factors/genetics/metabolism MH - Chromosome Mapping MH - *Chromosomes, Human, Pair 7 MH - Cloning, Molecular MH - Evolution, Molecular MH - Humans MH - Mice MH - Molecular Sequence Data MH - Multigene Family MH - Phylogeny MH - Receptors, CCR3 MH - Receptors, Chemokine/*metabolism MH - Recombinant Proteins/metabolism MH - Restriction Mapping MH - Transfection EDAT- 1999/09/17 00:00 MHDA- 1999/09/17 00:01 CRDT- 1999/09/17 00:00 PHST- 1999/09/17 00:00 [pubmed] PHST- 1999/09/17 00:01 [medline] PHST- 1999/09/17 00:00 [entrez] AID - 10.1074/jbc.274.39.27975 [doi] AID - S0021-9258(19)52210-4 [pii] PST - ppublish SO - J Biol Chem. 1999 Sep 24;274(39):27975-80. doi: 10.1074/jbc.274.39.27975.