Interactions of bacterial lipopolysaccharide and peptidoglycan with a 70 kDa and an 80 kDa protein on the cell surface of CD14(+) and CD14(-) cells

Bacterial cell wall components, lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN) are known to stimulate cells of the immune, inflammatory and vascular systems contributing to septic shock. CD14 has b een identified as the main LPS receptor, a process that is accelerated by t he serum protein LPS-binding protein (LBP). CD14 has also been found to bin d LTA and PGN from the cell wall of gram positive bacteria. Recently, toll- like receptor proteins TLR-2 and TLR-4 have been shown to be required for L PS and LTA-induced intracellular signalling. Although CD14 functions as eit her a glycosylphosphatidylinositol (GPI)anchored molecule that does not tra nsverse the cell membrane or as a soluble serum protein, the mechanisms by which the CD14-LPS/LTA complex interacts with the TLRs remains to be elucid ated. We have looked directly CD14-deprndent manner. Using biochemical appr oaches we have identified two proteins of molecular weight 70 kDa (LAP-1) a nd 80 kDa (LAP-2) that can be precipitated from both CD14(+) and CD14(-) ce lls with LPS- or LTA-specific antibodies. Binding of LPS and LTA to LAP-1 a nd -2 required serum. While soluble CD14 (sCD14) was sufficient to allow pr ecipitation of these two proteins from CD14(-) cells, serum could not be re placed by purified sCD14 and/or LBP when mCD14-expressing cells were used. Human Immunology 62, 50-63 (2001). (C) American Society for Histocompatibil ity and Immunogenetics, 2001. Published by Elsevier Science Inc.