EOTAXIN-2, A NOVEL CC CHEMOKINE THAT IS SELECTIVE FOR THE CHEMOKINE RECEPTOR CCR3, AND ACTS LIKE EOTAXIN ON HUMAN EOSINOPHIL AND BASOPHIL LEUKOCYTES

A novel human CC chemokine consisting of 78 amino acids and having a m olecular mass of 8,778.3 daltons (VVIPSPCCMF FVSKRIPENR VVSYQLSSRS TCL KAGVIFT TKKGQQ SCGD PKQEWVQRYM KNLDAKQKKA SPRARAVA) was isolated toget her with three minor COOH-terminally truncated variants with 73, 75, a nd 76 residues. The new chemokine was termed eotaxin-2 because it is f unctionally very similar to eotaxin. In terms of structure, however, e otaxin and eotaxin-2 are rather distant, they share only 39% identical amino acids and differ almost completely in the NH2-terminal region. Eotaxin-2 induced chemotaxis of eosinophils as well as basophils, with a typically bimodal concentration dependence, and the release of hist amine and leukotriene C-4 from basophils that had been primed with IL- 3. In all assays, eotaxin-2 had the same efficacy as eotaxin, but was somewhat less potent. The migration and the release responses were abr ogated in the presence of a monoclonal antibody that selectively block s the eotaxin receptor, CCR3, indicating that eotaxin-2, like eotaxin, acts exclusively via CCR3. Receptor usage was also studied in desensi tization experiments by measuring [Ca2+](i) changes in eosinophils. Co mplete cross-desensitization was observed between eotaxin-2, eotaxin a nd MCP-4 confirming activation via CCR3. No Ca2+ mobilization was obta ined in neutrophils, monocytes and lymphocytes, in agreement with the lack of chemotactic responsiveness. Intradermal injection of eotaxin-2 in a rhesus monkey (100 or 1,000 pmol per site) induced a marked loca l infiltration of eosinophils, which was most pronounced in the vicini ty of postcapillary venules and was comparable to the effect of eotaxi n.