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

Richard I. Tapping, Peter S. Tobias

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)23157-23164
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number37
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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