title: Cell-surface thioredoxin-1: possible involvement in thiol-mediated leukocyte-endothelial cell interaction through lipid rafts.
abstract: Human thioredoxin-1 (hTrx) exhibits a disulfide reducing activity and was originally identified as a soluble cytokine-like factor secreted from cells of a human T-cell leukemia virus type I (HTLV-I)-transformed cell line. Recent studies have revealed that endogenous Trx plays an important role in cytoprotection against various oxidative stress-associated disorders. However, the function of exogenous Trx is still not fully understood. We report here that a cysteine-modified mutant of recombinant human Trx (rhTrx-C35S) binds to human umbilical vein endothelial cells (HUVECs) as well as stimulated T cells and rapidly enters these cells via lipid rafts. In addition, we found that endogenous Trx is expressed on the surface of HUVECs, including lipid rafts. These events suggest cell-surface Trx as a possible target of rhTrx-C35S. Furthermore, we found that anti-human Trx mouse monoclonal antibody inhibits adherence of LPS-stimulated human peripheral blood polymorphonuclear cells (PMNs) to HUVECs. This adherence was also suppressed by a recombinant human Trx (rhTrx), but not by a mutant rhTrx (rhTrx-C32S/C35S) with no reducing activity. Cell-surface Trx may be involved in the process of interaction between PMNs and HUVECs and a possible target of cysteine-modified exogenous Trx as well as wild-type exogenous Trx through redox regulation.
authors.affiliation: Department of Biological Responses, Institute for Virus Research, Kyoto University, and Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tomijiro
authors.initials: T
authors.lastname: Hara
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kondo
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuyama
authors.forename: Akira
authors.initials: A
authors.lastname: Mitsui
authors.forename: Yuma
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D021962:Membrane Microdomains / Q000502:physiology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000502:physiology*; D018613:Microscopy, Confocal; D011994:Recombinant Proteins / Q000494:pharmacology; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D011994:Recombinant Proteins; D013879:Thioredoxins