Requirements for the different cysteines in the chemotactic and desensitizing activity of human thioredoxin

Thioredoxin (Trx) is a protein disulfide oxidoreductase that can be secreted and act as a chemoattractant for leukocytes. Like chemokines, it causes desensitization of monocytes against its chemotactic activity and that of monocyte chemoattractant protein-1 (MCP-1). To investigate the role of the re...

Full description

Saved in:
Bibliographic Details
Published inAntioxidants & redox signaling Vol. 7; no. 9-10; p. 1189
Main Authors Bizzarri, Cinzia, Holmgren, Arne, Pekkari, Klas, Chang, Geng, Colotta, Francesco, Ghezzi, Pietro, Bertini, Riccardo
Format Journal Article
LanguageEnglish
Published United States 01.09.2005
Subjects
Cell Movement
Chemokine CCL2 - metabolism
Chemokines - metabolism
Chemotaxis
Cysteine - chemistry
Cysteine - metabolism
Cysteine - physiology
Dose-Response Relationship, Drug
Humans
Leukocytes, Mononuclear - cytology
Monocytes - cytology
Monocytes - metabolism
Mutation
N-Formylmethionine Leucyl-Phenylalanine - pharmacology
Neutrophils - metabolism
Oxidation-Reduction
Peptides - chemistry
Recombinant Proteins - chemistry
Thioredoxins - chemistry
Thioredoxins - genetics
Thioredoxins - metabolism
Online AccessGet more information

Cover

More Information
Summary:Thioredoxin (Trx) is a protein disulfide oxidoreductase that can be secreted and act as a chemoattractant for leukocytes. Like chemokines, it causes desensitization of monocytes against its chemotactic activity and that of monocyte chemoattractant protein-1 (MCP-1). To investigate the role of the redox properties of Trx, and particularly of some of its five cysteines, in its chemotactic and desensitizing action, we tested different mutants, including Trx80, a truncated form, and various mutants lacking specific cysteines: Trx C62S/C73S and the redox-inactive mutant Trx C32S/C35S. Of the mutants, only Trx80 maintained the chemotactic activity of wild-type Trx toward both monocytes and polymorphonuclear neutrophils, all of them desensitized monocytes against wild-type Trx or MCP-1, but not chemotactic peptide formyl-methionyl-leucil peptide. These data indicate that different redox-active cysteines are important for Trx chemotactic action, whereas its desensitizing action does not have these requirements, suggesting a redox-independent mechanism.
ISSN:1523-0864
1557-7716
DOI:10.1089/ars.2005.7.1189