RELEASE FROM A HUMAN MONOCYTE-LIKE CELL-LINE OF 2 DIFFERENT SOLUBLE FORMS OF THE LIPOPOLYSACCHARIDE RECEPTOR, CD14

Lipopolysaccharide (LPS) stimulates mononuclear phagocytes to synthesi ze and secrete immunoregulatory and inflammatory molecules such as int erleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha). LPS forms complexes with either the serum protein termed LPS-binding p rotein or a serum factor, septin. These complexes are more stimulatory than LPS alone. The myeloid differentiation antigen CD14 is known to be the receptor for such complexes. In the present study, by using a m onocytic cell line, we demonstrate the release of two different solubl e forms of CD14 (sCD14) which are secreted by different mechanisms. We show that the two sCD14 forms differ in their electrophoretic mobilit y, two-dimensional gel electrophoretic patterns, sensitivity to endogl ycosidases and peptide maps. One of the sCD14 molecules, apparent mole cular mass 48 kDa, was found in supernatants of both surface iodinated and [S-35]methionine biosynthetically labeled cells. The other sCD14 molecule (56 kDa) was found labeled only in supernatants of [S-35]meth ionine-labeled cells. Furthermore, purified 48 kDa sCD14 enhanced the LPS-induced TNF-alpha and IL-6 release by the monocytic cells suggesti ng that a cell-surface signal transducer molecule may be involved in s ignaling. The data suggest a possible novel role for sCD14 in the mono cyte response to LPS.