Soluble CD14 enhances membrane CD14-mediated responses to peptidoglycan: Structural requirements differ from those for responses to lipopolysaccharide

The purpose of this study was to identify the functional significance of th e binding of soluble CD14 (sCD14) to bacterial peptidoglycan (PGN) and to c ompare the structural requirements of sCD14 for the binding to PGN and lipo polysaccharide (LPS) and for sCD14-mediated enhancement of PGN- and LPS-ind uced cell responses. sCD14 did not facilitate the responses of membrane CD1 4 (mCD14)-negative pre-B 70Z/3 cells to PGN, although it facilitated the re sponses of these cells to LPS and although mCD14 facilitated the responses of 70Z/3 cells to PGN. sCD14 enhanced mCD14-mediated cell activation by bot h PGN and LPS, but only the responses to LPS, and not to PGN, were enhanced by LPS-binding protein. Four 4- or 5-amino-acid-long sequences within the 65-amino-acid N-terminal region of sCD14 were needed for binding to both PG N and LPS and for enhancement of cell activation by both PGN and LPS. Howev er, deletions of individual sequences had different effects on the ability of sCD14 to bind to PGN and to LPS and on the ability to enhance the respon ses to PGN and to LPS. Thus, there are different structural requirements of sCD14 for binding to PGN and to LPS and for the enhancement of PGN- and LP S-induced cell activation.