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Effects of macrophage transplantation in the injured adult rat spinal cord: A combined immunocytochemical and biochemical study
Author(s) -
Franzen Rachelle,
Schoenen Jean,
Leprince Pierre,
Joosten Elbert,
Moonen Gustave,
Martin Didier
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19980201)51:3<316::aid-jnr5>3.0.co;2-j
Subject(s) - basic fibroblast growth factor , biology , remyelination , transplantation , glial fibrillary acidic protein , neurotrophic factors , glial scar , fibroblast growth factor , laminin , schwann cell , nerve growth factor , neurite , neurotrophin , pathology , myelin , microbiology and biotechnology , growth factor , extracellular matrix , spinal cord , immunology , spinal cord injury , central nervous system , medicine , endocrinology , immunohistochemistry , neuroscience , biochemistry , receptor , in vitro
Early and robust invasion by macrophages may be one of the reasons why axonal regeneration is more effective in the PNS than in the CNS. Therefore, we have grafted autologous peritoneal macrophages labeled with fluorescent latex microspheres into spinal cord compression lesions. At various survival times, we have studied their effect on the expression of neuronal (neurofilaments [NF], calcitonin gene‐related peptide [CGRP], 5‐hydroxytryptamine [5‐HT]) and nonneuronal markers (myelin‐associated glycoprotein [MAG], glial fibrillary acidic protein [GFAP], laminin) by using semiquantitative Western blot and immunohistochemical techniques. After 1 month, we observed a significant decrease of the expression of MAG as well as an important invasion of the lesion site by neurites, chiefly peptidergic axons of presumed dorsal root origin, in macrophage‐grafted animals compared with controls. In addition, angiogenesis and Schwann cell infiltration were more pronounced after macrophage grafts, providing an increase in laminin, a favorable substrate for axonal regrowth. By using reverse transcription‐polymerase chain reaction (RT‐PCR), mRNAs for tumor necrosis factor‐alpha (TNF‐α) were detected in the transplanted cells, whereas results were negative for nerve growth factor (NGF), neurotrophin‐3 (NT‐3), brain‐derived neurotrophic factor (BDNF), or acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF). Thus, macrophage grafts may represent an interesting strategy to promote axonal regeneration in the CNS. Our study suggests that they may exert their beneficial effects by degrading myelin products, which inhibit axonal regrowth, and by promoting a permissive extracellular matrix containing notably laminin. No evidence for a direct synthesis of neurotrophic factors by the transplanted macrophages was found in this study, but resident glial cells could secrete such factors as a result of stimulation by macrophage‐released cytokines. J. Neurosci. Res. 51:316–327, 1998. © 1998 Wiley‐Liss, Inc.