Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells.
Thioredoxin (Trx) is a ubiquitous intracellular protein disulfide oxidoreductase with a CXXC active site that can be released by various cell types upon activation. We show here that Trx is chemotactic for monocytes, polymorphonuclear leukocytes, and T lymphocytes, both in vitro in the standard micro Boyden chamber migration assay and in vivo in the mouse air pouch model. The potency of the chemotactic action of Trx for all leukocyte populations is in the nanomolar range, comparable with that of known chemokines. However, Trx does not increase intracellular Ca2+ and its activity is not inhibited by pertussis toxin. Thus, the chemotactic action of Trx differs from that of known chemokines in that it is G protein independent. Mutation of the active site cysteines resulted in loss of chemotactic activity, suggesting that the latter is mediated by the enzyme activity of Trx. Trx also accounted for part of the chemotactic activity released by human T lymphotropic virus (HTLV)-1-infected cells, which was inhibited by incubation with anti-Trx antibody. Since Trx production is induced by oxidants, it represents a link between oxidative stress and inflammation that is of particular interest because circulating Trx levels are elevated in inflammatory diseases and HIV infection.
Bertini
R
R
Dompé Research Center, 67100 L'Aquila, Italy.
Howard
O M
OM
Dong
H F
HF
Oppenheim
J J
JJ
Bizzarri
C
C
Sergi
R
R
Caselli
G
G
Pagliei
S
S
Romines
B
B
Wilshire
J A
JA
Mengozzi
M
M
Nakamura
H
H
Yodoi
J
J
Pekkari
K
K
Gurunath
R
R
Holmgren
A
A
Herzenberg
L A
LA
Herzenberg
L A
LA
Ghezzi
P
P
D000818:Animals; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology* / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D015490:HTLV-I Infections / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007239:Infections / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010084:Oxidation-Reduction; D013601:T-Lymphocytes / Q000502:physiology; D013879:Thioredoxins / Q000378:metabolism* / Q000494:pharmacology*
D002630:Chemotactic Factors; D013879:Thioredoxins