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.
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16 June 1997
Brief Definitive Report|
June 16 1997
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,
Ulf Forssmann
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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Mariagrazia Uguccioni,
Mariagrazia Uguccioni
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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Pius Loetscher,
Pius Loetscher
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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Clemens A. Dahinden,
Clemens A. Dahinden
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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Hanno Langen,
Hanno Langen
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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Marcus Thelen,
Marcus Thelen
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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Marco Baggiolini
Marco Baggiolini
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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Ulf Forssmann
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
Mariagrazia Uguccioni
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
Pius Loetscher
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
Clemens A. Dahinden
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
Hanno Langen
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
Marcus Thelen
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
Marco Baggiolini
From the *Theodor Kocher Institute, University of Bern, CH-3000 Bern, Switzerland; ‡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
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).
Received:
March 07 1997
Revision Received:
April 18 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (12): 2171–2176.
Article history
Received:
March 07 1997
Revision Received:
April 18 1997
Citation
Ulf Forssmann, Mariagrazia Uguccioni, Pius Loetscher, Clemens A. Dahinden, Hanno Langen, Marcus Thelen, Marco Baggiolini; Eotaxin-2, a Novel CC Chemokine that Is Selective for the Chemokine Receptor CCR3, and Acts Like Eotaxin on Human Eosinophil and Basophil Leukocytes. J Exp Med 16 June 1997; 185 (12): 2171–2176. doi: https://doi.org/10.1084/jem.185.12.2171
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