Monoclonal antibodies to murine lipopolysaccharide (LPS)-binding protein (LBP) protect mice from lethal endotoxemia by blocking either the binding of LPS to LBP or the presentation of LPS/LBP complexes to CD14.
J Immunol
; 162(12): 7454-60, 1999 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-10358200
ABSTRACT
Cellular responses to LPS, the major lipid component of the outer membrane of Gram-negative bacteria, are enhanced markedly by the LPS-binding protein (LBP), a plasma protein that transfers LPS to the cell surface CD14 present on cells of the myeloid lineage. LBP has been shown previously to potentiate the host response to LPS. However, experiments performed in mice with a disruption of the LBP gene have yielded discordant results. Whereas one study showed that LBP knockout mice were resistant to endotoxemia, another study did not confirm an important role for LBP in the response of mice challenged in vivo with low doses of LPS. Consequently, we generated rat mAbs to murine LBP to investigate further the contribution of LBP in experimental endotoxemia. Three classes of mAbs were obtained. Class 1 mAbs blocked the binding of LPS to LBP; class 2 mAbs blocked the binding of LPS/LBP complexes to CD14; class 3 mAbs bound LBP but did not suppress LBP activity. In vivo, class 1 and class 2 mAbs suppressed LPS-induced TNF production and protected mice from lethal endotoxemia. These results show that the neutralization of LBP accomplished by blocking either the binding of LPS to LBP or the binding of LPS/LBP complexes to CD14 protects the host from LPS-induced toxicity, confirming that LBP is a critical component of innate immunity.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Fase Aguda
/
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Lipopolissacarídeos
/
Apresentação de Antígeno
/
Receptores de Lipopolissacarídeos
/
Anticorpos Bloqueadores
/
Endotoxemia
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Anticorpos Monoclonais
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article