Expression of α2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP) in rat microglial cells

Maria Paz Marzolo, Rommy Von Bernhardi, Guojun Bu, Nibaldo C. Inestrosa

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Low density lipoprotein receptor-related protein (LRP) participates in the uptake and degradation of several ligands implicated in neuronal pathophysiology including apolipoprotein E (apoE), activated α2 - macroglobulin (α2M°) and β-amyloid precursor protein (APP). The receptor is expressed in a variety of tissues. In the brain LRP is present in pyramidal-type neurons in cortical and hippocampal regions and in astrocytes that are activated as a result of injury or neoplasmic transformation. As LRP is expressed in the monocyte/macrophage cell system, we were interested in examining whether LRP is expressed in microglia. We isolated glial cells from the brain of neonatal rats and LRP was immunodetected both in microglial cells and in astrocytes expressing glial fibrillar acidic protein (GFAP). Microglial cells were able to bind and internalize LRP-specific ligand, α2M°. The internalization was inhibitable by RAP, with a Kd of 1.7 nM. The expression of LRP was upregulated by dexamethasone, and down-regulated by lipopolysaccharide (LPS), gamma interferon (IFN-γ) or a combination of both. LRP was less sensitive to dexamethasone in activated astrocytes than in microglia. We provided the first analysis of LRP expression and regulation in microglia. Our results open the possibility that microglial cells could be related to the participation of LRP and its ligands in different pathophysiological states in brain. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)401-411
Number of pages11
JournalJournal of Neuroscience Research
Volume60
Issue number3
DOIs
StatePublished - May 1 2000

Keywords

  • Alpha-2 macroglobulin
  • Astrocyte
  • LRP
  • Microglia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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