Release from a human monocyte-like cell line of two different soluble forms of the lipopolysaccharide receptor, CD14.
Lipopolysaccharide (LPS) stimulates mononuclear phagocytes to synthesize and secrete immunoregulatory and inflammatory molecules such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha). LPS forms complexes with either the serum protein termed LPS-binding protein 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 monocytic cell line, we demonstrate the release of two different soluble forms of CD14 (sCD14) which are secreted by different mechanisms. We show that the two sCD14 forms differ in their electrophoretic mobility, two-dimensional gel electrophoretic patterns, sensitivity to endoglycosidases and peptide maps. One of the sCD14 molecules, apparent molecular mass 48 kDa, was found in supernatants of both surface iodinated and [35S]methionine biosynthetically labeled cells. The other sCD14 molecule (56 kDa) was found labeled only in supernatants of [35S]methionine-labeled cells. Furthermore, purified 48 kDa sCD14 enhanced the LPS-induced TNF-alpha and IL-6 release by the monocytic cells suggesting that a cell-surface signal transducer molecule may be involved in signaling. The data suggest a possible novel role for sCD14 in the monocyte response to LPS.
Labeta
M O
MO
Department of Research, University Hospital, Basel, Switzerland.
Durieux
J J
JJ
Fernandez
N
N
Herrmann
R
R
Ferrara
P
P
D015703:Antigens, CD / Q000032:analysis* / Q000096:biosynthesis / Q000737:chemistry; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis* / Q000096:biosynthesis / Q000737:chemistry; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D010449:Peptide Mapping; D011971:Receptors, Immunologic / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha