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Human peripheral nerve macrophages in normal and pathological conditions
B Bonetti1, S Monaco, C Giannini
1Institute of Neurology, University of Verona, Italy.
Abstract:
We investigated, by immunocytochemistry and immune electron microscopy, the immunophenotype, morphology and functional properties of human peripheral nervous system (PNS) macrophages (M phi) under normal and pathological conditions. Endoneurial M phi disclosed an elongated, ramified morphology, with the main processes oriented along the major axis of nerve fibers; they shared several lineage-related and functional markers with monocyte/macrophages and central nervous system (CNS) microglia, including CD4, CR3, CR4 and FcRIII. In addition, basal expression of HLA-DR antigens was exclusively confined to M phi in normal PNS. In the course of unrelated pathological conditions, resident M phi underwent activation with transformation to hypertrophic cells or foamy phagocytes and up-regulation of the markers expressed in normal conditions; new expression of a macrophagic antigen was detected on activated M phi. In different neuropathies, HLA-DR expression was also detected on non-myelin forming Schwann cells with ultrastructural features indicative of denervation. The present results demonstrate that the human PNS is provided with an intrinsic population of immunocompetent and potentially phagocytic M phi, which represent the peripheral counterpart of CNS microglia.
Insights
Human peripheral nervous system (PNS) macrophages (M phi) are immunocompetent cells, similar to central nervous system (CNS) microglia. These resident M phi play a role in nerve injury responses and express key immune markers.
Area of Science:
- Neuroimmunology
- Cell Biology
Background:
- Macrophages (M phi) in the human peripheral nervous system (PNS) have not been fully characterized.
- Understanding their phenotype and function is crucial for neuroinflammation research.
Purpose of the Study:
- To investigate the immunophenotype, morphology, and functional properties of human PNS macrophages.
- To compare PNS macrophages with central nervous system (CNS) microglia and monocytes.
Main Methods:
- Immunocytochemistry and immune electron microscopy were employed.
- Analysis of macrophage markers (CD4, CR3, CR4, FcRIII, HLA-DR) in normal and pathological conditions.
Main Results:
- Endoneurial M phi exhibit elongated morphology and share markers with monocytes and CNS microglia.
- Resident M phi are activated in pathological conditions, showing hypertrophy and phagocytosis.
- HLA-DR expression is found on M phi and, in neuropathies, on denervated Schwann cells.
Conclusions:
- The human PNS contains an intrinsic population of immunocompetent macrophages.
- These PNS macrophages are the peripheral counterparts of CNS microglia.
- PNS macrophages are involved in immune responses within the peripheral nervous system.