Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil- activating chemokine

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1994
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Dahinden, Clemens
Geiser, Thomas
Tscharner, Vinzenz von
Caput, Daniel
Ferrara, Pascual
Minty, Adrian
Baggiolini, Marco
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Journal of Experimental Medicine. 1994, 179(2), pp. 751-756. ISSN 0022-1007. Available under: doi: 10.1084/jem.179.2.751
Zusammenfassung

CC chemokines constitute a novel class of cytokines that attract and activate monocytes and lymphocytes, as well as basophil and eosinophil leukocytes, with distinct target cell profiles, and are believed to be involved in the regulation of different types of inflammation. The action of the recently identified monocyte chemotactic protein 3 (MCP-3) on human basophil and eosinophil function was studied and compared with that of other CC chemokines. In basophils, MCP-3, MCP-1, RANTES, and macrophage inflammatory protein (MIP)-1 alpha all induced cytosolic-free calcium concentration ([Ca2+]i) changes and, with different efficacies, chemotaxis (RANTES = MCP-3 > MCP-1 > MIP-1 alpha), histamine release (MCP-1 = MCP-3 > RANTES > MIP-1 alpha), and leukotriene C4 formation, after IL-3 pretreatment (MCP-1 = MCP-3 > RANTES > MIP-1 alpha). Thus, MCP-3 was as effective as MCP-1 as an inducer of mediator release, and as effective as RANTES as a stimulus of basophil migration. In contrast to MCP-1, MCP-3 was also a stimulus for eosinophils, and induced [Ca2+]i changes and chemotaxis as effectively as RANTES, which is the most potent chemotactic cytokine for these cells. Desensitization of the transient changes in [Ca2+]i was used to assess receptor usage. In basophils, stimulation with MCP-3 prevented responsiveness to MCP-1 and RANTES, but not to MIP-1 alpha. No single CC chemokine (except for MCP-3 itself) affected the response to MCP-3, however, which was prevented only when the cells were prestimulated with both MCP-1 and RANTES. In eosinophils, by contrast, cross-desensitization between RANTES and MCP-3 was obtained. RANTES and to a lesser extent MCP-3 also desensitized eosinophils toward MIP-1 alpha. The desensitization data suggest the existence of three chemokine receptors: (a) a MCP-1 receptor expressed on basophils but not eosinophils that is activated by MCP-1 and MCP-3; (b) a RANTES receptor in basophils and eosinophils that is activated by RANTES and MCP-3; and (c) a MIP-1 alpha receptor that is activated by MIP-1 alpha, RANTES and, more weakly, by MCP-3. This study shows that MCP-3 combines the properties of RANTES, a powerful chemoattractant, and MCP-1, a highly effective stimulus of mediator release, and thus has a particularly broad range of activities toward both human basophil and eosinophil leukocytes.

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570 Biowissenschaften, Biologie
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ISO 690DAHINDEN, Clemens, Thomas GEISER, Thomas BRUNNER, Vinzenz von TSCHARNER, Daniel CAPUT, Pascual FERRARA, Adrian MINTY, Marco BAGGIOLINI, 1994. Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil- activating chemokine. In: Journal of Experimental Medicine. 1994, 179(2), pp. 751-756. ISSN 0022-1007. Available under: doi: 10.1084/jem.179.2.751
BibTex
@article{Dahinden1994Monoc-16638,
  year={1994},
  doi={10.1084/jem.179.2.751},
  title={Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil- activating chemokine},
  number={2},
  volume={179},
  issn={0022-1007},
  journal={Journal of Experimental Medicine},
  pages={751--756},
  author={Dahinden, Clemens and Geiser, Thomas and Brunner, Thomas and Tscharner, Vinzenz von and Caput, Daniel and Ferrara, Pascual and Minty, Adrian and Baggiolini, Marco}
}
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