# Insulin-like growth factor-1/insulin-like growth factor-1 receptor signalling in macrophages facilitates recovery from acute lung injury

## TL;DR

This study shows that IGF-1 signaling in macrophages helps repair lung damage in a mouse model of acute lung injury, suggesting a new treatment for ARDS.

## Contribution

The study identifies IGF-1/IGF-1R signaling in macrophages as a novel mechanism promoting recovery from acute lung injury.

## Key findings

- IGF-1 administration reduced inflammation and lung injury in mice during recovery.
- IGF-1R was highly expressed on alveolar macrophages and improved efferocytosis.
- Blocking IGF-1R with JB1 counteracted the beneficial effects of IGF-1.

## Abstract

No effective treatment strategy for acute respiratory distress syndrome (ARDS) has been established. Conflicting reports on the effects of insulin-like growth factor (IGF)-1 stimulation and the inhibition of IGF-1 receptor (IGF-1R) signalling in tissue injury across several organs have led to hesitation in advancing IGF-1-based treatment strategies for tissue damage.

We aim to examine whether IGF-1/IGF-1R signalling contributes to recovery from acute lung injury in mouse models and to further explore its potential mechanisms.

Lipopolysaccharide (LPS) was intratracheally injected into mice to create acute lung injury models. Experiments were conducted to acquire or inhibit IGF-1 signalling through the intratracheal injection of recombinant IGF-1 or JB1, an IGF-1 receptor antagonist during the recovery phase of the models, starting on day 4 after LPS administration. Bone marrow monocyte-derived macrophages (MDMs) cocultured with IGF-1 and/or JB1 were intratracheally injected during the recovery phase.

Inflammatory cell counts and lung injury scores were significantly decreased when recombinant IGF-1 was administered in the later phase, while they increased with the administration of JB1. On day 4 after LPS injection, IGF-1 receptor (IGF-1R, also known as CD221) was strongly expressed on macrophages, particularly in CD11c+SiglecF+ alveolar macrophages (AMs). Intratracheal injection of MDMs cocultured with IGF-1 decreased lung neutrophil counts, whereas the addition of JB1 to MDMs cocultured with IGF-1 counteracted the effect of IGF-1. JB1 also reduced efferocytosis capacity of AMs in the later phase. In the phagocytosis assay, LPS decreased the efflux capacity of macrophages, but recombinant IGF-1 improved this capacity regardless of the presence or absence of LPS.

IGF-1/IGF-1R signalling in macrophage facilitates the recovery from acute lung injury via enhancing efferocytosis. IGF-1 delivery potentially offers a new treatment strategy for ARDS.