Presence and regulation of insulin-regulated aminopeptidase in mouse macrophages

Alexandros Nikolaou, Benoit Stijlemans, Damya Laoui, Elio Schouppe, Huyen Tran Thi Thanh, Dirk Tourwé, Siew Y Chai, Patrick M L Vanderheyden, Jo A Van Ginderachter

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

INTRODUCTION: 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)466-479
Number of pages14
JournalJournal of the Renin-Angiotensin-Aldosterone System
Volume15
Issue number4
DOIs
Publication statusPublished - Dec 2014

Keywords

  • 3T3-L1 Cells
  • Animals
  • Cell Membrane
  • Cystinyl Aminopeptidase
  • Gene Expression Regulation
  • Glucose
  • Inflammation
  • Interferon-gamma
  • Intracellular Space
  • Lectins, C-Type
  • Ligands
  • Lipopolysaccharides
  • Macrophage Activation
  • Macrophages, Peritoneal
  • Mannose-Binding Lectins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B
  • Phagocytosis
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface
  • Research Support, Non-U.S. Gov't

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