Related Experiment Video
Updated: Jun 15, 2026
Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Distinct migratory and cytokine responses of human microglia and macrophages to ATP
Caroline Lambert1, Ariel R Ase, Philippe Séguéla
1Neuroimmunology Unit, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
Abstract:
Microglia and hematogenous myeloid cells are prominent components of inflammatory central nervous system (CNS) lesions associated with tissue injury. To help define the basis for recruitment of such cells into lesions and their contribution to the disease process, we characterized the migratory and cytokine responses of human adult and fetal microglia in the presence of extracellular ATP comparing them to monocytes and macrophages. Adult microglia showed increased migration in response to low ATP concentrations (1-10 μM) whereas fetal microglia also migrated in response to higher ATP dosages (100-300 μM). The enhanced migration of microglia was reproduced with 2-MeSADP, a P2Y1/12/13 agonist. In contrast, the chemokine CCL2 did not promote migration of microglia, but promoted the migration of monocytes. Monocyte migration was also enhanced with low concentrations of ATP, whereas higher concentrations of ATP mediated an inhibitory effect. ATP had only an inhibitory effect on macrophages, which was not reproduced with hydrolysis products ADP or adenosine. ATP led to a decrease in LPS-induced pro-inflammatory cytokine release (TNFα, IL-6) in both microglia and macrophages without suppression of an anti-inflammatory response (IL-10). These in vitro based results suggest that ATP can selectively favor the recruitment of microglia rather than hematogenous myeloid cells while promoting an anti-inflammatory state in both hematogenous and resident myeloid cells of the CNS. Our results highlight the importance of environmental signals in shaping the properties of the innate immune response to injury in the CNS.
Insights
Extracellular ATP selectively recruits microglia to the central nervous system (CNS) and promotes an anti-inflammatory state in myeloid cells, influencing innate immune responses to CNS injury.
Area of Science:
- Neuroimmunology
- Cellular and Molecular Neuroscience
Background:
- Microglia and hematogenous myeloid cells are key players in central nervous system (CNS) inflammation and injury.
- Understanding their recruitment and function is crucial for developing effective therapies for CNS diseases.
Purpose of the Study:
- To investigate the differential migratory and cytokine responses of human microglia, monocytes, and macrophages to extracellular ATP.
- To elucidate the role of ATP in shaping the innate immune response within the CNS.
Main Methods:
- In vitro characterization of human adult and fetal microglia, monocytes, and macrophages.
- Assessment of cell migration in response to varying concentrations of extracellular ATP and agonists.
- Analysis of cytokine release (TNFα, IL-6, IL-10) following ATP stimulation.
Main Results:
- Adult microglia exhibited enhanced migration at low ATP concentrations (1-10 μM); fetal microglia responded to higher concentrations (100-300 μM).
- Monocyte migration was enhanced by low ATP but inhibited by high ATP; macrophages showed only ATP-mediated inhibition.
- ATP reduced pro-inflammatory cytokine release (TNFα, IL-6) in microglia and macrophages without affecting anti-inflammatory IL-10.
- Chemokine CCL2 promoted monocyte migration but not microglia migration.
Conclusions:
- Extracellular ATP selectively promotes microglia recruitment over hematogenous myeloid cells in the CNS.
- ATP induces an anti-inflammatory phenotype in both resident and infiltrating myeloid cells in the CNS.
- Environmental signals like ATP are critical in modulating innate immune responses to CNS injury.
