LIPOPOLYSACCHARIDE (LPS) SIGNAL-TRANSDUCTION AND CLEARANCE - DUAL ROLES FOR LPS BINDING-PROTEIN AND MEMBRANE CD14

Under physiological conditions, lipopolysaccharide (LPS) activation of cells involves the LPS binding protein (LBP) and either membrane or s oluble CD14. We find LPS forms a ternary complex with LBP and membrane CD14 (mCD14). Subsequent to complex formation and distinct from signa l transduction, LBP and LPS internalize, Internalization can be separa ted from signal transduction with the anti LBP antibody 18G4 and the a nti-CD14 antibody 18E12. 18G4 inhibits LBP binding to mCD14 without bl ocking signal transduction or LPS transfer to soluble CD14; 18E12 inhi bits signal transduction without affecting LPS binding and uptake. The se data show that while LPS signal transduction and LPS clearance util ize both LBP and mCD14, the pathways bifurcate after LPS binding to mC D14.