Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 28, Pages 7460-7467Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0023-06.2006
Keywords
chemotaxis; macrophage; nerve injury; pancreatitis; associated protein; PAP; regenerating gene; Reg; hepatocarcinoma-intestine-pancreas; HIP
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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.
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