PMID- 19395472
OWN - NLM
STAT- MEDLINE
DCOM- 20090902
LR  - 20211020
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 86
IP  - 2
DP  - 2009 Aug
TI  - Hemopexin down-regulates LPS-induced proinflammatory cytokines from macrophages.
PG  - 229-35
LID - 10.1189/jlb.1208742 [doi]
AB  - Detection of LPS in tissues is an integral component of innate immunity that acts 
      to protect against invasion by Gram-negative bacteria. Plasma down-regulates 
      LPS-induced cytokine production from macrophages, thereby limiting systemic 
      inflammation in blood and distant tissues. To identify the protein(s) involved in 
      this process, we used classical biochemical chromatographic techniques to 
      identify fractions of mouse sera that suppress LPS-induced TNF from bone 
      marrow-derived macrophages (BMDMs). Fractionation yielded microgram quantities of 
      a protein that was identified by MS to be hemopexin (Hx). Mouse Hx purified on 
      hemin-agarose beads and rhHx decreased the production of cytokines from BMDMs and 
      peritoneal macrophages induced by LPS. Preincubation of LPS with Hx did not 
      affect the activity of LPS on LAL, whereas preincubation of Hx with macrophages 
      followed by washing resulted in decreased activity of these cells in response to 
      LPS, suggesting that Hx acts on macrophages rather than LPS. Heme-free Hx did not 
      stimulate HO-1 in the macrophages. Purified Hx also decreased TNF and IL-6 from 
      macrophages induced by the synthetic TLR2 agonist Pam3Cys. Our data suggest that 
      Hx, which is an acute-phase protein that increases during inflammation, limits 
      TLR4 and TLR2 agonist-induced macrophage cytokine production directly through a 
      mechanism distinct from HO-1.
FAU - Liang, Xueya
AU  - Liang X
AD  - Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 
      USA.
FAU - Lin, Tian
AU  - Lin T
FAU - Sun, Guangjie
AU  - Sun G
FAU - Beasley-Topliffe, Laura
AU  - Beasley-Topliffe L
FAU - Cavaillon, Jean-Marc
AU  - Cavaillon JM
FAU - Warren, H Shaw
AU  - Warren HS
LA  - eng
GR  - AI059010/AI/NIAID NIH HHS/United States
GR  - GM59694/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090424
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Cytokines)
RN  - 0 (Dipeptides)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Lipoproteins)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9013-71-2 (Hemopexin)
RN  - 98598-79-9 (2,3-bis-(palmitoyloxy)-2-propyl-N-palmitoyl-cysteinylserine)
SB  - IM
CIN - J Leukoc Biol. 2009 Aug;86(2):203-4. PMID: 19643739
CIN - J Leukoc Biol. 2010 Jan;87(1):1-2; author reply 3, 5. PMID: 20047881
MH  - Acute-Phase Reaction/immunology/physiopathology
MH  - Animals
MH  - Bacterial Infections/complications/*immunology/physiopathology
MH  - Cytokines/*metabolism
MH  - Dipeptides/pharmacology
MH  - Down-Regulation/drug effects/immunology
MH  - Hemopexin/*metabolism/pharmacology
MH  - Immune Tolerance/drug effects/*immunology
MH  - Immunity, Innate/drug effects/immunology
MH  - Inflammation/*immunology/microbiology/physiopathology
MH  - Inflammation Mediators/metabolism/pharmacology
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides/immunology/pharmacology
MH  - Lipoproteins/pharmacology
MH  - Macrophages/drug effects/*immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Toll-Like Receptor 2/agonists/antagonists & inhibitors/metabolism
MH  - Toll-Like Receptor 4/agonists/antagonists & inhibitors/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC2726768
EDAT- 2009/04/28 09:00
MHDA- 2009/09/03 06:00
PMCR- 2010/08/01
CRDT- 2009/04/28 09:00
PHST- 2009/04/28 09:00 [entrez]
PHST- 2009/04/28 09:00 [pubmed]
PHST- 2009/09/03 06:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - jlb.1208742 [pii]
AID - 1208-742 [pii]
AID - 10.1189/jlb.1208742 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2009 Aug;86(2):229-35. doi: 10.1189/jlb.1208742. Epub 2009 Apr 24.