Pancreatitis-associated protein-III is a novel macrophage chemoattractant implicated in nerve regeneration.
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.
Namikawa
Kazuhiko
K
Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, Asahimachi, Osaka 545-8585, Japan.
Okamoto
Takashi
T
Suzuki
Akinobu
A
Konishi
Hiroyuki
H
Kiyama
Hiroshi
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002633:Chemotaxis; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D018014:Gene Transfer Techniques; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology; D008297:Male; D051379:Mice; D009416:Nerve Regeneration; D000073718:Pancreatitis-Associated Proteins; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000502:physiology
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C000612144:Reg3b protein, rat; C000612145:Reg3g protein, rat