Cell-surface thioredoxin-1: possible involvement in thiol-mediated leukocyte-endothelial cell interaction through lipid rafts.
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.
Hara
Tomijiro
T
Department of Biological Responses, Institute for Virus Research, Kyoto University, and Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
Kondo
Norihiko
N
Nakamura
Hajime
H
Okuyama
Hiroaki
H
Mitsui
Akira
A
Hoshino
Yuma
Y
Yodoi
Junji
J
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*
D008565:Membrane Proteins; D011994:Recombinant Proteins; D013879:Thioredoxins