Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 257-264 |
| Number of pages | 8 |
| Journal | Journal of Endotoxin Research |
| Volume | 6 |
| Issue number | 3 |
| State | Published - 2000 |
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ASJC Scopus subject areas
- Immunology
- Microbiology
- Toxicology
Cite this
Endotoxin-mimetic effect of antibodies against Toll-like receptor 4. / Nattermann, J.; Du, X.; Wei, Y.; Shevchenko, D.; Beutler, B.
In: Journal of Endotoxin Research, Vol. 6, No. 3, 2000, p. 257-264.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endotoxin-mimetic effect of antibodies against Toll-like receptor 4
AU - Nattermann, J.
AU - Du, X.
AU - Wei, Y.
AU - Shevchenko, D.
AU - Beutler, B.
PY - 2000
Y1 - 2000
N2 - 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.
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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033774091&partnerID=8YFLogxK
M3 - Article
C2 - 11052181
AN - SCOPUS:0033774091
VL - 6
SP - 257
EP - 264
JO - Innate Immunity
JF - Innate Immunity
SN - 1753-4259
IS - 3
ER -