%0 Journal Article %A Kazuhiko Namikawa %A Takashi Okamoto %A Akinobu Suzuki %A Hiroyuki Konishi %A Hiroshi Kiyama %T Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration %D 2006 %R 10.1523/JNEUROSCI.0023-06.2006 %J The Journal of Neuroscience %P 7460-7467 %V 26 %N 28 %X 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. %U https://www.jneurosci.org/content/jneuro/26/28/7460.full.pdf