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Volume 272, Number 37, Issue of September 12, 1997 pp. 23157-23164
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Cellular Binding of Soluble CD14 Requires Lipopolysaccharide (LPS) and LPS-binding Protein

(Received for publication, April 11, 1997, and in revised form, June 4, 1997)

Richard I. Tapping and Peter S. Tobias

From the Department of Immunology, IMM-12, The Scripps Research Institute, La Jolla, California 92037

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 radiolabeled 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-containing, 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.


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