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Microglial migration mediated by ATP-induced ATP release from lysosomes.
- Source :
- Cell Research; Jun2012, Vol. 22 Issue 6, p1022-1033, 12p
- Publication Year :
- 2012
-
Abstract
- Microglia are highly motile cells that act as the main form of active immune defense in the central nervous system. Attracted by factors released from damaged cells, microglia are recruited towards the damaged or infected site, where they are involved in degenerative and regenerative responses and phagocytotic clearance of cell debris. ATP release from damaged neural tissues has been suggested to mediate the rapid extension of microglial process towards the site of injury. However, the mechanisms of the long-range migration of microglia remain to be clarified. Here, we found that lysosomes in microglia contain abundant ATP and exhibit Ca<superscript>2+</superscript>-dependent exocytosis in response to various stimuli. By establishing an efficient in vitro chemotaxis assay, we demonstrated that endogenously-released ATP from microglia triggered by local microinjection of ATPĪ³S is critical for the long-range chemotaxis of microglia, a response that was significantly inhibited in microglia treated with an agent inducing lysosome osmodialysis or in cells derived from mice deficient in Rab 27a (ashen mice), a small GTPase required for the trafficking and exocytosis of secretory lysosomes. These results suggest that microglia respond to extracellular ATP by releasing ATP themselves through lysosomal exocytosis, thereby providing a positive feedback mechanism to generate a long-range extracellular signal for attracting distant microglia to migrate towards and accumulate at the site of injury. [ABSTRACT FROM AUTHOR]
- Subjects :
- MICROGLIA
CELLS
CENTRAL nervous system
ADENOSINE triphosphate
WOUNDS & injuries
Subjects
Details
- Language :
- English
- ISSN :
- 10010602
- Volume :
- 22
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Cell Research
- Publication Type :
- Academic Journal
- Accession number :
- 76303440
- Full Text :
- https://doi.org/10.1038/cr.2012.10