A single dose of angiotensin-(1–7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge

Abstract

Objective

Angiotensin-(1–7) [Ang-(1–7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1–7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge.

Methods

Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1–7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed.

Results

Treatment with Ang-(1–7) resulted in elevated levels of IL-10, CD4⁺Foxp3⁺, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1–7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1–7) effectively prevented the lung inflammation.

Conclusion

A single dose of Ang-(1–7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.