Relève étoile Jacques-Genest 
September 2020



Ju Jing Tan

PhD student in Biomedical Science
CRCHUM, Université de Montréal

Award-winning publicationType 2 secretory cells are primary source of ATP release in mechanically stretched lung alveolar cells

Published in: American Journal of Physiology
 

Abstract

Adenosine triphosphate (ATP) is known for its role in transporting energy within cells. However, outside cells, ATP acts as an extracellular signaling molecule—a key element of the purinergic signaling pathway. In the lungs, ATP prompts the secretion of surfactant, which expands the alveoli and facilitates breathing. In light of this critical role, it is important to understand the mechanism by which cellular ATP is released. Because mechanical forces are the main trigger, the project aimed to elucidate the physiological mechanisms and cell sources of this release in alveoli, which are chiefly made up of types 1 (AT1) and 2 (AT2) alveolar cells. To do so, freshly isolated AT2 cells from the lungs of rats were seeded on a flexible silicone chamber and maintained for seven days, during which they progressively transformed into AT1 cells. Ju Jing Tan's findings show that the amount of ATP that is released decreases along with the quantity of AT2 cells, thus indicating that the cells are the main source of ATP release in response to stretching. The addition of pharmacological ATP pathway modulators does not lower the quantity of ATP that is released, though the addition of an intracellular calcium chelator led to a significant reduction. The modulators have similar effects on intracellular calcium responses, thus suggesting a connection between ATP release and calcium. As a whole, these results show that ATP release does not occur through ATP pathways and rather depends on intracellular calcium. The study will make it possible to better characterize purinergic signaling in organs that are constantly exposed to physical constraints and could potentially lead to therapeutic targets that will modulate the negative impacts of the excessive ATP released observed in a number of pathological conditions and in ventilator-induced lung injuries in particular.