title: IFN-gamma up-regulates the human C5a receptor (CD88) in myeloblastic U937 cells and related cell lines.
abstract: On human mature monocytes the immunomodulator IFN-gamma has been shown to down-regulate the receptor for the anaphylatoxic peptide C5a (CD88, C5aR). In this study, we show that in immature myelo-/monoblastic U937, HL60, and MonoMac6 cells, IFN-gamma induces C5aR-ligand binding activity. In U937 cells, this induction cannot be blocked by the protein kinase C inhibitor staurosporine. An increase in free cytosolic Ca2+ upon ligand binding indicates functional coupling of this receptor in U937 and HL-60 cells. G-Proteins involved in this C5a responsiveness after IFN-gamma induction are completely pertussis toxin sensitive. Our data suggest that an additional pertussis toxin-resistant pathway exists in U937 cells after induction by dibutyryl cAMP. However, this is not due to changes in the mRNA level of the pertussis toxin-insensitive G-protein subunit G alpha 16. Induction by dibutyryl cAMP, but not that by IFN-gamma, resulted in C5a-dependent release of N-acetyl-beta-D-glucosaminidase, further highlighting functional differences in the effects of the inducers. Our data show an IFN-gamma-dependent increase in C5aR expression and suggest a maturation-related change in signaling of the C5aR, presumably at the level of receptor coupling.
authors.affiliation: Institute for Medical Microbiology, Medical College of Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Burg
authors.forename: U
authors.initials: U
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Rheinheimer
authors.forename: J
authors.initials: J
authors.lastname: Köhl
authors.forename: W
authors.initials: W
authors.lastname: Bautsch
authors.forename: E C
authors.initials: EC
authors.lastname: Böttger
authors.forename: A
authors.initials: A
authors.lastname: Klos
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D015703:Antigens, CD / Q000187:drug effects*; D001667:Binding, Competitive; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D015936:Complement C5a / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005456:Fluorescent Dyes; D016257:Fura-2; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016403:Lymphoma, Large B-Cell, Diffuse; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D037342:Pertussis Toxin; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D005456:Fluorescent Dyes; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D010566:Virulence Factors, Bordetella; D003994:Bucladesine; D015936:Complement C5a; D007371:Interferon-gamma; D037342:Pertussis Toxin; D000118:Acetylglucosaminidase; D019204:GTP-Binding Proteins; D016257:Fura-2