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The disulfide bond between cysteine 10 and cysteine 34 is required for CCL18 activity.

Abstract
Asthma is a Th2-mediated disease that involves Th2 cell and eosinophil migration into the bronchial mucosa which is dependent upon the expression of a specific set of chemokines within the lung. Among them, CCL18 seems to play a key role because of its preferential expression in the lung, and its up-regulation by Th2 cytokines. Here, we show that the optimal naïve T cell and basophil chemotaxis, and basophil histamine release induced by rhCCL18 occurred at a 100 time lower concentration with CHO-derived rhCCL18 than with E. coli-derived rhCCL18. FT-ICR mass spectrometry of the intact chemokines showed that the rhCCL18 produced by CHO cells contained the 2 disulfide bonds Cys10-Cys34 and Cys11-Cys50, in clear contrast to the rhCCL18 derived from E. coli where the Cys10-Cys34 bond was absent. We found that reduction of the Cys10-Cys34 of the CHO-derived rhCCL18 resulted in a shift of its activity, reaching the same level as the E. coli-derived rhCCL18. These results demonstrate that the Cys10-Cys34 disulfide bond is involved in the function of CCL18.
AuthorsBenjamin Legendre, Caroline Tokarski, Ying Chang, Nathalie De Freitas Caires, Hugues Lortat-Jacob, Patricia De Nadaï, Christian Rolando, Catherine Duez, Anne Tsicopoulos, Philippe Lassalle
JournalCytokine (Cytokine) Vol. 64 Issue 1 Pg. 463-70 (Oct 2013) ISSN: 1096-0023 [Electronic] England
PMID23742785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Ltd. All rights reserved.
Chemical References
  • CCL18 protein, human
  • Chemokines, CC
  • Histamine
  • Cysteine
Topics
  • Animals
  • Asthma (immunology, metabolism)
  • Basophils (immunology, metabolism)
  • CHO Cells
  • Cell Line
  • Cell Movement (immunology)
  • Chemokines, CC (chemistry, genetics, metabolism)
  • Cricetulus
  • Cysteine (chemistry, genetics)
  • Eosinophils (metabolism)
  • Histamine (immunology)
  • Histamine Release
  • Humans
  • Lung (immunology)
  • Th2 Cells (immunology)

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