Vesicle-mediated transport and release of CCL21 in endangered neurons: A possible explanation for microglia activation remote from a primary lesion

EK de Jong, IM Dijkstra, M Hensens, N Brouwer, M van Amerongen, RSB Liem, HWGM Boddeke, K Biber*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

109 Citations (Scopus)

Abstract

Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to understand how microglia activity is controlled. The remote activation of microglia implies that the activating signals are transported along neuronal projections. However, the identity of these signals has not yet been identified. It is shown here that glutamate-treated neurons rapidly express and release the chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in vesicles and transported throughout neuronal processes to reach presynaptic structures. Chemotaxis assays show that functional CCL21 is released from endangered neurons and activate microglia via the chemokine receptor CXCR3. Based on these findings, we suggest that neuronal CCL21 is important in directed neuron-microglia signaling and that this communication could account for the remote activation of microglia, far distant from a primary lesion.

Original languageEnglish
Pages (from-to)7548-7557
Number of pages10
JournalThe Journal of Neuroscience
Volume25
Issue number33
Publication statusPublished - 17-Aug-2005

Keywords

  • neuron-microglia signaling
  • chemokines
  • CCL21
  • vesicle release
  • apoptosis
  • neuroinflammation
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • CENTRAL-NERVOUS-SYSTEM
  • LYMPHOID CHEMOKINES CCL19
  • CLASS-II INDUCIBILITY
  • MACROPHAGE RECRUITMENT
  • FUNCTIONAL EXPRESSION
  • REGULATED SECRETION
  • GOLGI NETWORK
  • TNF-ALPHA
  • IN-VITRO

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