Adenosine Triphosphate Release From Influenza-Infected Lungs Enhances Neutrophil Activation and Promotes Disease Progression

Background Adenosine triphosphate (ATP) enhances neutrophil responses, but little is known about the role of ATP in influenza infections.Methods We used a mouse influenza model to study if ATP release is associated with neutrophil activation and disease progression.Results Influenza infection increased pulmonary ATP levels 5-fold and plasma ATP levels 3-fold vs healthy mice. Adding ATP at those concentrations to blood from healthy mice primed neutrophils and enhanced CD11b and CD63 expression, CD62L shedding, and reactive oxygen species production in response to formyl peptide receptor stimulation. Influenza infection also primed neutrophils in vivo, resulting in formyl peptide receptor-induced CD11b expression and CD62L shedding up to 3 times higher than that of uninfected mice. In infected mice, large numbers of neutrophils entered the lungs. These cells were significantly more activated than the peripheral neutrophils of infected mice and pulmonary neutrophils of healthy mice. Plasma ATP levels of infected mice and influenza disease progression corresponded with the numbers and activation level of their pulmonary neutrophils.Conclusions Findings suggest that ATP release from the lungs of infected mice promotes influenza disease progression by priming peripheral neutrophils, which become strongly activated and cause pulmonary tissue damage after their recruitment to the lungs. Influenza infection releases adenosine triphosphate that primes peripheral neutrophils and causes their excessive activation after they infiltrate the lungs. Thus, adenosine triphosphate-induced neutrophil priming may be a therapeutic target to reduce lung tissue damage in severe influenza cases.

Automated summary

The study suggests that ATP release from the lungs of infected mice promotes influenza disease progression by priming peripheral neutrophils, which become strongly activated and cause pulmonary tissue damage after their recruitment to the lungs. This finding highlights ATP-induced neutrophil priming as a potential therapeutic target for reducing lung tissue damage in severe influenza cases.