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Updated: Jan 26, 2026

Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Intercellular Calcium Signaling Induced by ATP Potentiates Macrophage Phagocytosis
Sara Zumerle1, Bianca Calì1, Fabio Munari1
1Department of Biomedical Sciences, University of Padova, Padova, Italy; Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.
Abstract:
Extracellular ATP is a signaling molecule exploited by the immune cells for both autocrine regulation and paracrine communication. By performing live calcium imaging experiments, we show that triggered mouse macrophages are able to propagate calcium signals to resting bystander cells by releasing ATP. ATP-based intercellular communication is mediated by P2X4 and P2X7 receptors and is a feature of pro-inflammatory macrophages. In terms of functional significance, ATP signaling is required for efficient phagocytosis of pathogen-derived molecules and apoptotic cells and may represent a target for macrophage regulation by CD39-expressing cells. These results highlight a cell-to-cell communication mechanism tuning innate immunity.
Insights
Immune cells like macrophages release extracellular ATP to communicate, triggering calcium signals in neighboring cells. This ATP signaling, mediated by P2X receptors, is crucial for innate immunity and phagocytosis.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Extracellular ATP (adenosine triphosphate) acts as a crucial signaling molecule in immune responses.
- Immune cells, particularly macrophages, utilize ATP for both self-regulation (autocrine) and communication with other cells (paracrine).
Purpose of the Study:
- To investigate the role of extracellular ATP in intercellular communication between mouse macrophages.
- To elucidate the mechanisms and functional significance of ATP-mediated signaling in innate immunity.
Main Methods:
- Live calcium imaging experiments were performed on triggered and resting mouse macrophages.
- Analysis of ATP release and its effects on bystander cells.
- Investigation of the involvement of P2X4 and P2X7 receptors in ATP signaling.
Main Results:
- Triggered mouse macrophages release ATP, propagating calcium signals to resting bystander cells.
- ATP-based intercellular communication is mediated by P2X4 and P2X7 receptors.
- This signaling pathway is characteristic of pro-inflammatory macrophages and is essential for efficient phagocytosis of pathogens and apoptotic cells.
Conclusions:
- Extracellular ATP is a key mediator of cell-to-cell communication in innate immunity, particularly involving macrophages.
- ATP signaling via P2X receptors plays a vital role in regulating immune cell function, including phagocytosis.
- This mechanism highlights a potential target for therapeutic modulation of macrophage-driven immune responses, possibly involving CD39-expressing cells.
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