PMID- 16115022 OWN - NLM STAT- MEDLINE DCOM- 20060104 LR - 20131121 IS - 1523-0864 (Print) IS - 1523-0864 (Linking) VI - 7 IP - 9-10 DP - 2005 Sep-Oct TI - Requirements for the different cysteines in the chemotactic and desensitizing activity of human thioredoxin. PG - 1189-94 AB - 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. FAU - Bizzarri, Cinzia AU - Bizzarri C AD - Dompe' Research Center and Consorzio Biolaq, L'Aquila, Italy. FAU - Holmgren, Arne AU - Holmgren A FAU - Pekkari, Klas AU - Pekkari K FAU - Chang, Geng AU - Chang G FAU - Colotta, Francesco AU - Colotta F FAU - Ghezzi, Pietro AU - Ghezzi P FAU - Bertini, Riccardo AU - Bertini R LA - eng PT - Journal Article PL - United States TA - Antioxid Redox Signal JT - Antioxidants & redox signaling JID - 100888899 RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Peptides) RN - 0 (Recombinant Proteins) RN - 52500-60-4 (Thioredoxins) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - K848JZ4886 (Cysteine) SB - IM MH - Cell Movement MH - Chemokine CCL2/metabolism MH - Chemokines/metabolism MH - *Chemotaxis MH - Cysteine/chemistry/metabolism/*physiology MH - Dose-Response Relationship, Drug MH - Humans MH - Leukocytes, Mononuclear/cytology MH - Monocytes/cytology/metabolism MH - *Mutation MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophils/metabolism MH - Oxidation-Reduction MH - Peptides/chemistry MH - Recombinant Proteins/chemistry MH - Thioredoxins/*chemistry/genetics/metabolism EDAT- 2005/08/24 09:00 MHDA- 2006/01/05 09:00 CRDT- 2005/08/24 09:00 PHST- 2005/08/24 09:00 [pubmed] PHST- 2006/01/05 09:00 [medline] PHST- 2005/08/24 09:00 [entrez] AID - 10.1089/ars.2005.7.1189 [doi] PST - ppublish SO - Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1189-94. doi: 10.1089/ars.2005.7.1189.