Cellular binding of soluble CD14 requires lipopolysaccharide (LPS) and LPS-binding protein

The stimulation of nonmyeloid cells by lipopolysaccharide (LPS) is mediated by the serum protein, soluble CD14 (sCD14), We have examined the interaction of sCD14 with whole cells using a biologically active radio labeled sCD14 molecule as a ligand, Specific binding of sCD14 to nonmyeloid cells is detected only when it is first incubated with both LPS and the serum LPS-binding protein (LBP), Through the use of an anti-CD14 monoclonal antibody, we demonstrate that sCD14 must interact with LPS in order for cellular binding to occur. Although LBP is traditionally known to function as a catalyst in the transfer of LPS to sCD14, our results reveal that LBP is actually a physical part of sCD14-c ontaining, cell-associating complexes. The LPS- and LBP-dependent cell surface binding of sCD14 appears to be distinct from events leading to cell stimulation, since certain anti-CD14 and anti-LBP monoclonal antibodies have different effects on cellular binding versus cellular activation, Bound sCD14 is internalized, indicating that the LBP- and LPS dependent binding of sCD14 may represent a novel general mechanism by which nonmyeloid cells clear LPS.