The role of macrophages in immune-mediated damage to the peripheral nervous system.
Macrophage-mediated segmental demyelination is the pathological hallmark of autoimmune demyelinating polyneuropathies, including the demyelinating form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. Macrophages serve a multitude of functions throughout the entire pathogenetic process of autoimmune neuropathy. Resident endoneurial macrophages are likely to act as local antigen-presenting cells by their capability to express major histocompatibility complex antigens and costimulatory B7-molecules, and may thus be critical in triggering the autoimmune process. Hematogenous infiltrating macrophages then find their way into the peripheral nerve together with T-cells by the concerted action of adhesion molecules, matrix metalloproteases and chemotactic signals. Within the nerve, macrophages regulate inflammation by secreting several pro-inflammatory cytokines including IL-1, IL-6, IL-12 and TNF-alpha. Autoantibodies are likely to guide macrophages towards their myelin or primarily axonal targets, which then attack in a complement-dependent and receptor-mediated manner. In addition, non-specific tissue damage occurs through the secretion of toxic mediators and cytokines. Later, macrophages contribute to the termination of inflammation by promoting T-cell apoptosis and expressing anti-inflammatory cytokines including TGF-beta1 and IL-10. During recovery, they are tightly involved in allowing Schwann cell proliferation, remyelination and axonal regeneration to proceed. Macrophages, thus, play dual roles in autoimmune neuropathy, being detrimental in attacking nervous tissue but also salutary, when aiding in the termination of the inflammatory process and the promotion of recovery.
Kiefer
R
R
Department of Neurology, Westfälische Wilhelms-Universität, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany. kieferr@uni-muenster.de
Kieseier
B C
BC
Stoll
G
G
Hartung
H P
HP
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology*; D017933:Peripheral Nervous System / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D011129:Polyradiculoneuropathy / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology
D016207:Cytokines