PMID- 11742067
OWN - NLM
STAT- MEDLINE
DCOM- 20020122
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 26
DP  - 2001 Dec 18
TI  - Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil 
      chemotaxis.
PG  - 15143-8
AB  - Thioredoxin (Trx), a redox enzyme with a conserved active site 
      (Cys-32-Gly-Pro-Cys-35), is induced and secreted into circulation in response to 
      inflammation. Studies here demonstrate that elevating Trx levels in circulation 
      either by i.v. injection of recombinant Trx or stimulating Trx release in 
      Trx-transgenic mice dramatically blocks lipopolysaccharide (LPS)-stimulated 
      neutrophil migration in the murine air pouch chemotaxis model. Furthermore, we 
      show that leukocyte recruitment induced by the murine chemokines KC/GROalpha, 
      RANTES (regulated upon activation, normal T cell expressed and secreted), and 
      monocyte chemoattractant protein-1 (MCP-1) is suppressed also in Trx-transgenic 
      mice. Addressing the mechanism responsible for this suppression, we show that 
      circulating Trx blocks (i) the LPS-stimulated in vitro activation of neutrophil 
      p38 mitogen-activated protein kinase, (ii) the normal down-regulation of CD62L on 
      neutrophils migrating into the LPS-stimulated air pouch, and (iii) the in vitro 
      adhesion of LPS-activated neutrophils on endothelial cells. However, as we also 
      show, Trx does not alter the expression of endothelial cell adhesion molecules 
      (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD62P, and 
      CD62E) within 3 h. Collectively, these findings indicate that elevated levels of 
      circulating Trx interfere with chemotaxis by acting directly on neutrophils. We 
      discuss these findings in the context of recent studies reporting beneficial 
      effects of acutely elevated Trx in ischemic injury and negative effects 
      associated with chronically elevated Trx in HIV disease.
FAU - Nakamura, H
AU  - Nakamura H
AD  - Department of Biological Responses, Institute for Virus Research, Kyoto 
      University, 53 Shogoin-Kawaharacho, Sakyo, Kyoto 606-8507, Japan. 
      hnakamur@virus.kyoto-u.ac.jp
FAU - Herzenberg, L A
AU  - Herzenberg LA
FAU - Bai, J
AU  - Bai J
FAU - Araya, S
AU  - Araya S
FAU - Kondo, N
AU  - Kondo N
FAU - Nishinaka, Y
AU  - Nishinaka Y
FAU - Herzenberg, L A
AU  - Herzenberg LA
FAU - Yodoi, J
AU  - Yodoi J
LA  - eng
GR  - CA-42509/CA/NCI NIH HHS/United States
GR  - CA-81543/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20011211
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Lipopolysaccharides)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/physiology
MH  - Chemokine CCL2/physiology
MH  - Chemokine CCL5/physiology
MH  - Chemotaxis, Leukocyte/*physiology
MH  - Down-Regulation/drug effects
MH  - Enzyme Activation
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Animal
MH  - Neutrophils/*drug effects/physiology
MH  - Thioredoxins/administration & dosage/*blood/genetics
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC64997
EDAT- 2001/12/14 10:00
MHDA- 2002/01/23 10:01
PMCR- 2002/06/18
CRDT- 2001/12/14 10:00
PHST- 2001/12/14 10:00 [pubmed]
PHST- 2002/01/23 10:01 [medline]
PHST- 2001/12/14 10:00 [entrez]
PHST- 2002/06/18 00:00 [pmc-release]
AID - 191498798 [pii]
AID - 4987 [pii]
AID - 10.1073/pnas.191498798 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15143-8. doi: 
      10.1073/pnas.191498798. Epub 2001 Dec 11.