title: The CD14 differentiation antigen mediates the development of endotoxin responsiveness during differentiation of mononuclear phagocytes.
abstract: The CD14 antigen was originally described as a differentiation antigen on mononuclear cells. The purpose of this study was to investigate the relationship between the appearance of surface CD14 and the acquisition of lipopolysaccharide (LPS) responsiveness during maturation of mononuclear phagocytes. Immature THP-1 cells responded poorly to LPS in the absence or presence of serum. Treatment with the maturational agent calcitriol caused a dose- and time-dependent increase in CD14 mRNA and surface CD14 and enhanced the responsiveness of THP-1 cells to smooth and rough form LPS, complexes of LPS and lipopolysaccharide-binding protein (LBP), and LPS in low concentrations of serum. Monoclonal antibodies to CD14 blocked the responses of THP-1 to LPS, LPS-LBP complexes and LPS in serum. Immunodepletion of LBP from serum also inhibited the effect of LPS in serum. The data show that maturation of the response of THP-1 cells to LPS and LPS-LBP complexes depends on the appearance of CD14 on the cell surface. Maturation of the response to LPS in serum depends in large part on the appearance of CD14 on the cell surface and the presence of LBP in serum.
authors.affiliation: Research Service, Seattle Department of Veterans Affairs Medical Center, WA.
authors.forename: T R
authors.initials: TR
authors.lastname: Martin
authors.forename: S M
authors.initials: SM
authors.lastname: Mongovin
authors.forename: P S
authors.initials: PS
authors.lastname: Tobias
authors.forename: J C
authors.initials: JC
authors.lastname: Mathison
authors.forename: A M
authors.initials: AM
authors.lastname: Moriarty
authors.forename: D J
authors.initials: DJ
authors.lastname: Leturcq
authors.forename: R J
authors.initials: RJ
authors.lastname: Ulevitch
mesh_terms: D000199:Actins / Q000032:analysis / Q000235:genetics; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001798:Blood Proteins / Q000032:analysis / Q000494:pharmacology; D018821:CD18 Antigens; D002454:Cell Differentiation / Q000502:physiology; D002762:Cholecalciferol / Q000494:pharmacology; D003470:Culture Media / Q000032:analysis / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000032:analysis / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000032:analysis / Q000494:pharmacology; D008969:Molecular Sequence Data; D010586:Phagocytes / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001798:Blood Proteins; D018821:CD18 Antigens; D003470:Culture Media; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002762:Cholecalciferol; D004247:DNA