UC San Diego

Background

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 over the levels in healthy mice. Adding ATP at those concentrations to blood from healthy mice primed their neutrophils and enhanced CD11b and CD63 expression, CD62L shedding, and reactive oxygen species production in response to formyl peptide receptor (FPR) stimulation. Influenza infection also primed neutrophils in vivo, resulting in FPR-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 peripheral neutrophils of infected 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.

Conclusion

Our findings suggest that ATP release from the lungs of infected mice promotes influenza disease progression by priming peripheral neutrophils that become strongly activated and cause pulmonary tissue damage after their recruitment to the lungs.