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Published on: March 30, 2018
Pancreatitis-associated protein-III is a novel macrophage chemoattractant implicated in nerve regeneration
Kazuhiko Namikawa1, Takashi Okamoto, Akinobu Suzuki
1Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, Asahimachi, Osaka 545-8585, Japan.
Abstract:
Circulating macrophages are recruited to degenerating nerves in response to nerve injury to remove myelin and axonal debris, a process that is crucial for successful nerve regeneration. In this study, we demonstrate that pancreatitis-associated protein (PAP)-III is a macrophage chemoattractant that is induced in and released from injured nerves. In vitro experiments revealed that PAP-III possessed a strong macrophage chemoattractant activity that was comparable with that of monocyte chemoattractant protein-1. In addition, gene knockdown via adenovirus-mediated small interference RNA expression in isolated sciatic nerves successfully suppressed PAP-III expression and its macrophage chemoattractant activity. Furthermore, overexpression or knockdown of the PAP-III gene in crushed sciatic nerves in rats resulted in acceleration or retardation of macrophage recruitment and subsequent nerve regeneration, respectively. Collectively, our results demonstrate that PAP-III is a novel macrophage chemoattractant that is involved in peripheral nerve regeneration and further provide new insights into Schwann cell-macrophage interactions and therapeutic interventions.
Insights
Pancreatitis-associated protein (PAP)-III attracts macrophages to injured nerves, aiding nerve regeneration. This discovery offers new therapeutic targets for nerve repair and Schwann cell-macrophage interactions.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Macrophage recruitment to injured nerves is vital for clearing debris and enabling nerve regeneration.
- The specific molecular signals that attract macrophages to damaged peripheral nerves are not fully understood.
Purpose of the Study:
- To identify novel chemoattractants involved in peripheral nerve regeneration.
- To investigate the role of pancreatitis-associated protein (PAP)-III in macrophage recruitment to injured nerves.
Main Methods:
- In vitro assessment of PAP-III's macrophage chemoattractant activity compared to monocyte chemoattractant protein-1.
- Adenovirus-mediated gene knockdown of PAP-III in isolated rat sciatic nerves.
- In vivo manipulation (overexpression and knockdown) of PAP-III in a rat sciatic nerve crush injury model.
Main Results:
- PAP-III demonstrated significant macrophage chemoattractant activity, comparable to MCP-1.
- Suppression of PAP-III expression reduced macrophage chemoattractant activity in vitro.
- PAP-III manipulation in vivo modulated macrophage recruitment and nerve regeneration rates.
Conclusions:
- PAP-III is a novel macrophage chemoattractant induced by nerve injury.
- PAP-III plays a crucial role in regulating macrophage infiltration and peripheral nerve regeneration.
- PAP-III represents a potential therapeutic target for enhancing nerve repair.
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