Abstract |
Despite significant progress in understanding the origin of soluble CD14 ( sCD14), its physiological function remains largely unknown. Recent research has produced contradictory observations suggesting that sCD14 may have either beneficial or detrimental properties in protection against LPS-induced endotoxin shock. To resolve this controversy and to establish a mouse model suitable for elucidation of the functions of human CD14 (hCD14) in vivo, we generated several lines of transgenic mice bearing different copy numbers of the hCd14 transgene on a murine Cd14-/- background. The hCD14 was entirely capable of complementing loss of mouse CD14 to mediate cellular responses to LPS. Serum levels of sCD14 in a founder with multiple copies of the transgene were several times higher than in transgenic animals with a single copy of Cd14. Furthermore, mice with high levels of hCD14 were hypo-responsive to LPS and survived a lethal dose of LPS. Further inquiry into the mechanism of the hypo-response to LPS revealed that protection is associated with the higher amounts of circulating LPS. Most of this circulating LPS can be immunoprecipitated with anti-CD14 antibodies. These results suggest that sCD14 blocks circulating LPS by limiting the amount of monocyte-bound LPS and thus reduces inflammatory responses.
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Authors | Berri Jacque, Kristin Stephan, Irina Smirnova, Bobae Kim, Damian Gilling, Alexander Poltorak |
Journal | European journal of immunology
(Eur J Immunol)
Vol. 36
Issue 11
Pg. 3007-16
(Nov 2006)
ISSN: 0014-2980 [Print] Germany |
PMID | 17039565
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Lipopolysaccharide Receptors
- Lipopolysaccharides
- Tumor Necrosis Factors
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Topics |
- Animals
- Disease Models, Animal
- Humans
- Lipopolysaccharide Receptors
(blood, genetics, immunology)
- Lipopolysaccharides
(antagonists & inhibitors, blood, immunology)
- Mice
- Mice, Transgenic
- Monocytes
(immunology)
- Shock, Septic
(genetics, immunology)
- Solubility
- Tumor Necrosis Factors
(analysis, metabolism)
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