Prostaglandin D2 synthase modulates macrophage activity and accumulation in injured peripheral nerves

Autor: Cristina Rivellini, Giorgia Serena Gullotta, Marco Bacigaluppi, Carla Taveggia, Maria Grazia Forese, Angelo Quattrini, Marta Pellegatta, Paola Podini, Paolo Canevazzi, Stefano C. Previtali
Rok vydání: 2019
Předmět:
Zdroj: Glia. 68:95-110
ISSN: 1098-1136
0894-1491
DOI: 10.1002/glia.23705
Popis: We have previously reported that prostaglandin D2 Synthase (L-PGDS) participates in peripheral nervous system (PNS) myelination during development. We now describe the role of L-PGDS in the resolution of PNS injury, similarly to other members of the prostaglandin synthase family, which are important for Wallerian degeneration (WD) and axonal regeneration. Our analyses show that L-PGDS expression is modulated after injury in both sciatic nerves and dorsal root ganglia neurons, indicating that it might play a role in the WD process. Accordingly, our data reveals that L-PGDS regulates macrophages phagocytic activity through a non-cell autonomous mechanism, allowing myelin debris clearance and favoring axonal regeneration and remyelination. In addition, L-PGDS also appear to control macrophages accumulation in injured nerves, possibly by regulating the blood-nerve barrier permeability and SOX2 expression levels in Schwann cells. Collectively, our results suggest that L-PGDS has multiple functions during nerve regeneration and remyelination. Based on the results of this study, we posit that L-PGDS acts as an anti-inflammatory agent in the late phases of WD, and cooperates in the resolution of the inflammatory response. Thus, pharmacological activation of the L-PGDS pathway might prove beneficial in resolving peripheral nerve injury.
Databáze: OpenAIRE