Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia

Ingo Bechmann, Jana Goldmann, Adam D Kovac, Erik Kwidzinski, Eva Simbürger, Frederick Naftolin, Ulrich Dirnagl, Robert Nitsch, Josef Priller

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we demonstrate the infiltration of blood-derived monocytic cells and their morphologic transformation into microglia in zones of acute, anterograde (Wallerian) axonal degeneration induced by entorhinal cortex lesion (ECL). ECL was performed in mice which had received green fluorescent protein (GFP)-transduced bone marrow grafts allowing identification of blood-derived elements within the brain. While in the unlesioned hemisphere GFP+ cells were restricted to perivascular and leptomeningeal sites, many round fluorescent cells appeared in hippocampal zones of axonal degeneration at 24 h post lesion (hpl). Within 72 hpl, these GFP+ cells acquired ramified, microglia-like morphologies, which persisted for at least 7 days post ECL. Differentiation of GFP+ cells into glial fibrillary acidic protein (GFAP)+ astrocytes was never observed. To exclude that this recruitment is an artifact of irradiation or bone marrow transplantation, the fluorescent cell tracker 6-carboxylfluorescein diacetate (CFDA) was injected into spleens of normal mice 1 day before ECL. Again, fluorescent cells appeared at the lesion site and along the layers of axonal degeneration at 48 hpl and CFDA+/MAC-1+, cells exhibited amoeboid and ramified morphologies. Thus, blood-derived cells infiltrate not only the site of mechanical lesion, but also the layers of anterograde axonal degeneration, where they readily transform into microglia-like elements. A role for infiltrating leukocytes in facilitating or modulating postlesional plasticity, e.g., by phagocytosis of growth-inhibiting myelin should now be considered. Moreover, monocytic cells may serve as vehicles to transport therapeutic substances such as neurotrophic factors or caspase inhibitors to zones of axonal degeneration.

Original languageEnglish
Pages (from-to)647-9
Number of pages3
JournalThe FASEB Journal
Volume19
Issue number6
DOIs
Publication statusPublished - Apr 2005

Keywords

  • Animals
  • Astrocytes
  • Axonal Transport
  • Axons
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Cell Differentiation
  • Entorhinal Cortex
  • Fluoresceins
  • Fluorescent Dyes
  • Gene Expression
  • Glial Fibrillary Acidic Protein
  • Green Fluorescent Proteins
  • Hematopoietic Stem Cells
  • Leukocytes, Mononuclear
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia
  • Transfection
  • Wallerian Degeneration
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia'. Together they form a unique fingerprint.

Cite this