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(Received for publication, April 11, 1997, and in revised form, June 4, 1997)
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.
Volume 272, Number 37,
Issue of September 12, 1997
pp. 23157-23164
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
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