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Transformation of donor‐derived bone marrow precursors into host microglia during autoimmune CNS inflammation and during the retrograde response to axotomy
Author(s) -
Flügel Alexander,
Bradl Monika,
Kreutzberg Georg W.,
Graeber Manuel B.
Publication year - 2001
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/jnr.1198
Subject(s) - microglia , axotomy , parenchyma , bone marrow , pathology , population , biology , inflammation , immune system , central nervous system , medicine , immunology , neuroscience , environmental health
Macrophages in the brain can have a triple source. They may originate from recently blood‐derived precursors, from the largely resident perivascular cell population (perivascular macrophages and related cells), and from intrinsic parenchymal as well as perivascular microglia. Although continuous exchange of part of the perivascular cell population with bone marrow‐derived precursors is now accepted, the turnover of adult parenchymal microglia has remained enigmatic. Using bone‐marrow chimeras carrying an unexpressed marker gene and carbon labeling of peripheral monocyte/macrophages in a combined model of facial nerve axotomy and transfer experimental autoimmune encephalitis, we demonstrate for the first time that there is an easy to induce exchange between parenchymal central nervous system (CNS) microglia and the macrophage precursor cell pool of the bone marrow. Furthermore, very low level infiltration of the CNS parenchyma by recently bone marrow‐derived microglia could be observed after simple peripheral nerve axotomy that is followed by neuronal regeneration. Thus, microglial cells can be considered wanderers between the peripheral immune system and the CNS where they may act as a “Trojan horse” in infections. The fact that recently bone marrow‐derived parenchymal microglia fully integrate into a regenerating brain nucleus' architecture encourages entirely new approaches for delivering genes into the adult CNS. J. Neurosci. Res. 66:74–82, 2001. © 2001 Wiley‐Liss, Inc.