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The Journal of Neuroscience, July 12, 2006, 26(28):7460-7467; doi:10.1523/JNEUROSCI.0023-06.2006

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Development/Plasticity/Repair
Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

Kazuhiko Namikawa,^1,2 Takashi Okamoto,¹ Akinobu Suzuki,¹ Hiroyuki Konishi,¹ and Hiroshi Kiyama¹

¹Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan, and ²Department of Functional Anatomy and Neuroscience, Asahikawa Medical College, Asahikawa 078-8510, Japan

Correspondence should be addressed to Dr. Hiroshi Kiyama, Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan. Email: kiyama{at}med.osaka-cu.ac.jp

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.

Key words: chemotaxis; macrophage; nerve injury; pancreatitis-associated protein; PAP; regenerating gene; Reg; hepatocarcinoma–intestine–pancreas; HIP

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Received Jan. 4, 2006; revised June 11, 2006; accepted June 12, 2006.

Correspondence should be addressed to Dr. Hiroshi Kiyama, Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan. Email: kiyama{at}med.osaka-cu.ac.jp

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				D. Viterbo, M. H. Bluth, Y.-y. Lin, C. M. Mueller, R. Wadgaonkar, and M. E. Zenilman Pancreatitis-Associated Protein 2 Modulates Inflammatory Responses in Macrophages J. Immunol., August 1, 2008; 181(3): 1948 - 1958. [Abstract] [Full Text] [PDF]

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