SOLUBLE LIPOPOLYSACCHARIDE RECEPTOR (CD14) IS RELEASED VIA 2 DIFFERENT MECHANISMS FROM HUMAN MONOCYTES AND CD14 TRANSFECTANTS

The receptor for lipopolysaccharide LPS (CD14) exists in a membrane-as sociated (mCD14) and a soluble form (sCD14). Previous studies indicate that monocytes produce sCD14 by limited proteolysis of the membrane-b ound receptor. In this study we demonstrate that human monocytes also produce sCD14 by a protease-independent mechanism. To investigate the molecular nature of this second pathway we studied sCD14 formation in the monocytic cell line Mono Mac 6 (MM6) and in CD14 transfectants. Bo th MM6 and the CD14 transfectants constitutively produce sCD14 by a pr otease-independent mechanism. Structural analysis of sCD14 produced by the CD14 transfectants reconfirmed the presence of the CO OH terminus predicted from the cDNA. Since glycosylphosphatidylinositol anchor at tachment is associated with the removal of a hydrophobic C-terminal si gnal peptide, our finding demonstrates that the transfectants secrete sCD14 which escaped this posttranslational modification. Identical res ults obtained for sCD14 derived from peritoneal dialysis fluid of a pa tient with kidney dysfunction show the in vivo relevance of this pathw ay for sCD14 production.