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Pleiotrophin Cellular Localization in Nerve Regeneration after Peripheral Nerve Injury

Brigitte Blondet, Gilles Carpentier, Fouad Lafdil and Jose Courty

Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires FRE CNRS N^o 2412, Université Paris XII, Créteil, France (BB,GC,JC), and Unité INSERM 581, "Remodelage tissulaire et fibrose" Hôpital Henri Mondor, Créteil, France (FL)

Correspondence to: Brigitte Blondet, Laboratoire CRRET, FRE CNRS N^o 2412, Université Paris XII, Avenue du Général de Gaulle, 94010 Créteil, France. E-mail: blondet{at}univ-paris12.fr

Pleiotrophin (PTN) is a member of the family of heparin-binding growth factors that displays mitogenic activities and promotes neurite outgrowth in vitro. In vivo, PTN is widely expressed along pathways of developing axons during the late embryonic and early postnatal period. Although the level of PTN gene expression is very low during adulthood, activation of the gene may occur during recovery from injury and seems to play an important role in tissue regeneration processes. In this study, we investigated whether PTN was involved in the regenerative process of injured peripheral nerves. To refer localization of the fluorescent markers to myelinated axons, we developed a specific computer tool for colocalization of fluorescence images with phase contrast images. Immunohistochemical analysis showed PTN in different types of nonneural cells in distal nerve segments, including Schwann cells, macrophages, and endothelial cells, but not in axons. Schwann cells exhibited PTN immunoreactivity as early as 2 days after injury, whereas PTN-positive macrophages were found 1 week later. Strong PTN immunoreactivity was noted in endothelial cells at all time points. These findings support the idea that PTN participates in the adaptive response to peripheral nerve injury. A better understanding of its contribution may suggest new strategies for enhancing peripheral nerve regeneration.

(J Histochem Cytochem 53:971–977, 2005)

Key Words: pleiotrophin • heparin affin regulatory • peptide • peripheral nervous system • recovery • Schwann cells • macrophages • endothelial cells

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