LBP IN ENDOTOXEMIA

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. Due to its essential role in the mediation of the presentation of LPS to CD14 and in the ensuing cytokine response,1,2 the acute-phase LBP was found to contribute to enhanced LPS-induced lethality in wild-type mice treated with anti-LBP antibodies (Table 1). This was observed with rabbit antibodies against mouse LBP3 as well as with two classes of rat monoclonal antibodies to mouse LBP: class 1 mAbs blocking the binding of LPS to LBP; and class 2 mAbs blocking the binding of LPS/LBP com-plexes to CD14.4 Class 1 and class 2 mAbs suppressed LPS-induced TNF production and protected mice from lethal endotoxemia. Experiments using mice with a disruption of the LBP gene have yielded conflicting results. In one study, the dis-ruption of the LBP gene was associated with suppression © W. S. Maney & Son LtdJournal of Endotoxin Research, Vol. 7, No. 6, 2001 Proceedings CD14 and LBP in endotoxemia and infections caused by Gram-negative bacteri