ROS-activated CXCR2+ neutrophils recruited by CXCL1 delay denervated skeletal muscle atrophy and undergo P53-mediated apoptosis

Neutrophils are the earliest master inflammatory regulator cells recruited to target tissues after direct infection or injury. Although inflammatory factors are present in muscle that has been indirectly disturbed by peripheral nerve injury, whether neutrophils are present and play a role in the associated inflammatory process remains unclear. Here, intravital imaging analysis using spinning-disk confocal intravital microscopy was employed to dynamically identify neutrophils in denervated muscle. Slice digital scanning and 3D-view reconstruction analyses demonstrated that neutrophils escape from vessels and migrate into denervated muscle tissue. Analyses using reactive oxygen species (ROS) inhibitors and flow cytometry demonstrated that enhanced ROS activate neutrophils after denervation. Transcriptome analysis revealed that the vast majority of neutrophils in denervated muscle were of the CXCR2 subtype and were recruited by CXCL1. Most of these cells gradually disappeared within 1 week via P53-mediated apoptosis. Experiments using specific blockers confirmed that neutrophils slow the process of denervated muscle atrophy. Collectively, these results indicate that activated neutrophils are recruited via chemotaxis to muscle tissue that has been indirectly damaged by denervation, where they function in delaying atrophy. Nerve injury: Immune cells defend against muscle wasting Live animal imaging experiments reveal how rapid recruitment of a subset of immune cells helps prevent muscle wasting after peripheral nerve injury. Such injuries take considerable time to heal, and there are no therapies that reliably prevent wasting of muscle lacking nervous innervation. Researchers led by JunJian Jiang and Jianguang Xu at Fudan University, Shanghai, China, have used intravital microscopy to record the cellular and molecular events that follow nerve damage in live mice. They observed heightened production of chemicals that summon immune cells known as neutrophils to the site of the injury. Even though the surrounding muscle cells were initially undamaged in this animal model, the recruited neutrophils delayed subsequent muscle wasting. This neutrophil recruitment was transient, but therapies that elicit a more sustained response could provide durable protection against muscle wasting.

Automated summary

This study used intravital microscopy to observe the dynamic cellular and molecular events following nerve damage. The researchers found that even though the surrounding muscle cells were initially undamaged in this animal model, rapid recruitment of neutrophils delayed subsequent muscle wasting. These findings reveal the immune cell defense mechanism against muscle wasting after peripheral nerve injury.