The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/6/2171/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 12, June 16, 1997 2171-2176

Brief Definitive Reports

Eotaxin-2, a Novel CC Chemokine that Is Selective for the Chemokine Receptor CCR3, and Acts Like Eotaxin on Human Eosinophil and Basophil Leukocytes

Ulf Forssmann*, Mariagrazia Uguccioni*, Pius Loetscher*,{ddagger}, Clemens A. Dahinden§, Hanno Langen||, Marcus Thelen*, and Marco Baggiolini*

From the * Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; {ddagger} Division of Rheumatology, University Hospital, CH-3010 Bern, Switzerland; § Institute of Immunology and Allergology, University Hospital, CH-3010 Bern, Switzerland; and || Hoffmann-La Roche Ltd., Basel, Switzerland

A novel human CC chemokine consisting of 78 amino acids and having a molecular mass of 8,778.3 daltons (VVIPSPCCMF FVSKRIPENR VVSYQLSSRS TCLKAGVIFT TKKGQQ SCGD PKQEWVQRYM KNLDAKQKKA SPRARAVA) was isolated together with three minor COOH-terminally truncated variants with 73, 75, and 76 residues. The new chemokine was termed eotaxin-2 because it is functionally very similar to eotaxin. In terms of structure, however, eotaxin 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 histamine and leukotriene C4 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 abrogated in the presence of a monoclonal antibody that selectively blocks the eotaxin receptor, CCR3, indicating that eotaxin-2, like eotaxin, acts exclusively via CCR3. Receptor usage was also studied in desensitization experiments by measuring [Ca2+]i changes in eosinophils. Complete cross-desensitization was observed between eotaxin-2, eotaxin and MCP-4 confirming activation via CCR3. No Ca2+ mobilization was obtained 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 local infiltration of eosinophils, which was most pronounced in the vicinity of postcapillary venules and was comparable to the effect of eotaxin.

Address correspondence to Marco Baggiolini, Theodor Kocher Institute, PO Box, CH-3000 Bern 9, Switzerland.

Donor blood buffy coats were provided by the Swiss Central Laboratory Blood Transfusion Service, SRK. This work was supported by Grant 31-39744.93 of the Swiss National Science Foundation (to M. Baggiolini).


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