title: Presence and regulation of insulin-regulated aminopeptidase in mouse macrophages.
abstract: BACKGROUND
  The insulin-regulated aminopeptidase (IRAP) is expressed in several cell types, where it is mainly located in specialized secretory endosomes that are quickly recruited to the cell surface upon cell type-specific activation. Here we describe for the first time the expression and subcellular distribution of IRAP in macrophages.
  
  
  METHODS
  IRAP mRNA expression, protein expression and presence at the cell surface was investigated by real-time polymerase chain reaction (PCR), Western blot and [(3)H]IVDE77 binding, respectively.
  
  
  RESULTS
  IRAP mRNA expression was increased by interferon-γ (IFN-γ) and lipopolysaccharide (LPS), but not by anti-inflammatory cytokines (interleukin (IL)-4, IL-10, transforming growth factor β (TGF-β)). IFN-γ increased [(3)H]IVDE77 binding steadily over time, while LPS quickly and transiently recruited IRAP to the cell surface. Combined stimulations with IFN-γ and LPS showed the same pattern as LPS alone. Latex particles also induced a transient recruitment of IRAP to the cell surface, but no difference was observed in phagocytic uptake between wild-type and IRAP(-/-) macrophages, suggesting that the enzymatic activity of IRAP is not required for the ingestion of particles.
  
  
  CONCLUSIONS
  IRAP is more highly expressed in pro-inflammatory M1-activated macrophages and its presence at the cell surface is modulated upon exposure to IFN-γ, LPS or exogenous particles.
authors.affiliation: Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Belgium Cellular and Molecular Immunology Unit, Vrije Universiteit Brussel, Belgium.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Nikolaou
authors.affiliation: Myeloid Cell Immunology Laboratory, VIB, Belgium Cellular and Molecular Immunology Unit, Vrije Universiteit Brussel, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Stijlemans
authors.affiliation: Myeloid Cell Immunology Laboratory, VIB, Belgium Cellular and Molecular Immunology Unit, Vrije Universiteit Brussel, Belgium.
authors.forename: Damya
authors.initials: D
authors.lastname: Laoui
authors.affiliation: Myeloid Cell Immunology Laboratory, VIB, Belgium Cellular and Molecular Immunology Unit, Vrije Universiteit Brussel, Belgium.
authors.forename: Elio
authors.initials: E
authors.lastname: Schouppe
authors.affiliation: Myeloid Cell Immunology Laboratory, VIB, Belgium Cellular and Molecular Immunology Unit, Vrije Universiteit Brussel, Belgium.
authors.forename: Huyen T T
authors.initials: HT
authors.lastname: Tran
authors.affiliation: Laboratory of Organic Chemistry, Vrije Universiteit Brussel, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
authors.affiliation: Department of Physiology, Monash University, Australia.
authors.forename: Siew Y
authors.initials: SY
authors.lastname: Chai
authors.affiliation: Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Belgium pvandhey@vub.ac.be.
authors.forename: Patrick M L
authors.initials: PM
authors.lastname: Vanderheyden
authors.affiliation: Myeloid Cell Immunology Laboratory, VIB, Belgium Cellular and Molecular Immunology Unit, Vrije Universiteit Brussel, Belgium.
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D010122:Cystinyl Aminopeptidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D008024:Ligands; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D007371:Interferon-gamma; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase; D005947:Glucose
keywords: Angiotensin IV; IVDE77; M1; insulin-regulated aminopeptidase; macrophage