PMID- 11052181
OWN - NLM
STAT- MEDLINE
DCOM- 20001114
LR  - 20061115
IS  - 0968-0519 (Print)
IS  - 0968-0519 (Linking)
VI  - 6
IP  - 3
DP  - 2000
TI  - Endotoxin-mimetic effect of antibodies against Toll-like receptor 4.
PG  - 257-64
AB  - Monospecific, affinity-purified polyclonal antibodies reacting with the 
      amino-terminal half of the mouse Toll-like receptor 4 (Tlr4) ectodomain failed to 
      block LPS effects and, to the contrary, were capable of inducing TNF synthesis 
      when applied to mouse macrophages and cross-linked with a secondary antibody. 
      This effect was observed with macrophages derived from C3H/HeN and C57BL/10ScSn 
      mice, but not with macrophages derived from C3H/HeJ or C57BL/10ScCr mice, 
      indicating a specific, Tlr4-dependent effect. Neither primary nor secondary 
      antibody caused any response if administered in the absence of the other reagent, 
      nor was any response observed in cells from mice lacking Tlr4, or bearing the 
      Lps(d) mutation of Tlr4. These findings support several conclusions. Tlr4, the 
      essential transducer of LPS responses, may act independently of LPS itself. LPS 
      needs not be internalized, nor must it bind to a secondary target within the cell 
      in order to exert its effect; rather, the receptor alone is required for 
      initiation of a signal. The data are consistent with the hypothesis that a 
      conformational change in Tlr4 is required for activation via this receptor, and 
      reveal that the amino-terminal half of the Tlr4 ectodomain is a target sufficient 
      for antibody-mediated activation.
FAU - Nattermann, J
AU  - Nattermann J
AD  - Department of Internal Medicine, UT Southwestern Medical Center, The Howard 
      Hughes Medical Institute, Dallas, Texas, USA.
FAU - Du, X
AU  - Du X
FAU - Wei, Y
AU  - Wei Y
FAU - Shevchenko, D
AU  - Shevchenko D
FAU - Beutler, B
AU  - Beutler B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Endotoxin Res
JT  - Journal of endotoxin research
JID - 9433350
RN  - 0 (Antibodies)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Endotoxins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antibodies/*pharmacology
MH  - Cell Line
MH  - Cells, Cultured
MH  - *Drosophila Proteins
MH  - Endotoxins/*antagonists & inhibitors/pharmacology
MH  - Macrophages, Peritoneal
MH  - Membrane Glycoproteins/biosynthesis/genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Molecular Mimicry
MH  - Receptors, Cell Surface/biosynthesis/genetics/*immunology
MH  - Recombinant Proteins/immunology
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - Tumor Necrosis Factor-alpha/immunology
EDAT- 2000/10/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/29 11:00
PHST- 2000/10/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/29 11:00 [entrez]
PST - ppublish
SO  - J Endotoxin Res. 2000;6(3):257-64.