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Published on: September 7, 2019
A role for Nogo receptor in macrophage clearance from injured peripheral nerve
Elizabeth J Fry1, Carole Ho, Samuel David
1Center for Research in Neuroscience, The McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec, Canada.
Abstract:
We report a role for Nogo receptors (NgRs) in macrophage efflux from sites of inflammation in peripheral nerve. Increasing numbers of macrophages in crushed rat sciatic nerves express NgR1 and NgR2 on the cell surface in the first week after injury. These macrophages show reduced binding to myelin and MAG in vitro, which is reversed by NgR siRNA knockdown and by inhibiting Rho-associated kinase. Fourteen days after sciatic nerve crush, regenerating nerves with newly synthesized myelin have fewer macrophages than cut/ligated nerves that lack axons and myelin. Almost all macrophages in the cut/ligated nerves lie within the Schwann cell basal lamina, while in the crushed regenerating nerves the majority migrate out. Furthermore, crush-injured nerves of NgR1- and MAG-deficient mice and Y-27632-treated rats show impaired macrophage efflux from Schwann cell basal lamina containing myelinated axons. These data have implications for the resolution of inflammation in peripheral nerve and CNS pathologies.
Insights
Nogo receptors (NgRs) regulate macrophage removal from injured peripheral nerves. Blocking NgRs impairs this efflux, impacting nerve inflammation resolution and CNS pathologies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Macrophage accumulation at injury sites is crucial for nerve repair but prolonged presence can hinder recovery.
- Nogo receptors (NgRs) are known to inhibit axonal regeneration after nerve injury.
- The role of NgRs in macrophage behavior at peripheral nerve injury sites remains unclear.
Purpose of the Study:
- To investigate the role of Nogo receptors (NgRs) in macrophage efflux from injured peripheral nerves.
- To determine if NgRs influence macrophage interaction with myelin and their migration out of the nerve.
Main Methods:
- Analyzing macrophage expression of NgR1 and NgR2 in rat sciatic nerves post-crush injury.
- In vitro assays to assess macrophage binding to myelin and MAG, with and without NgR modulation.
- Utilizing NgR1 and MAG-deficient mice, and Y-27632 treated rats to study macrophage efflux in vivo.
Main Results:
- Macrophages in injured rat sciatic nerves upregulate NgR1 and NgR2.
- NgR expression correlates with reduced macrophage binding to myelin and MAG, which is reversible.
- Impaired macrophage efflux from nerve tissue was observed in NgR-deficient or inhibited models.
Conclusions:
- Nogo receptors (NgRs) play a significant role in facilitating macrophage efflux from peripheral nerve injury sites.
- Modulating NgR activity could be a therapeutic strategy for enhancing inflammation resolution in nerve pathologies.
- Understanding NgR function in macrophages is critical for addressing peripheral nerve and CNS inflammatory conditions.
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