Artikel
Catecholaminergic-to-cholinergic transition of sympathetic nerve fibers is stimulated under healthy but not under inflammatory arthritic conditions
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Autoren
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Hubert Stangl
- Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I, Rheumatologie und Klinische Immunologie, Regensburg
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Robert H. Springorum
- Orthopädische Klinik für die Universität Regensburg, Asklepios Klinikum Bad Abbach, Orthopädie, Bad Abbach
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Dominique Muschter
- Universitätsklinikum Regensburg, Experimentelle Orthopädie, Zentrum für Medizinische Biotechnologie, Regensburg
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Susanne Grässel
- Universitätsklinikum Regensburg, Experimentelle Orthopädie, Zentrum für Medizinische Biotechnologie, Regensburg
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Rainer H. Straub
- University Hospital Regensburg, Lab. of Exp. Neuroendocrine Immunology and Rheumatology, Dept. of Internal Medicine, Regensburg
| Veröffentlicht: | 12. September 2014 |
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Gliederung
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Background: Sympathetic nerve fibers play an important role in arthritic inflammation. Density of catecholaminergic sympathetic nerve fibers decreases in inflamed tissue tested by immunoreactivity towards tyrosine hydroxylase (TH, key enzyme of catecholamine synthesis). Since sympathetic nerve fibers can change phenotype from catecholaminergic to cholinergic (example: sweat gland innervation), loss of nerve fibers may relate to undetectable TH. The study aimed to investigate possible catecholaminergic-to-cholinergic transition of sympathetic nerve fibers using tissue of animals with arthritis, and patients with rheumatoid arthritis (RA) and osteoarthritis (OA).
Methods: Nerve fibers were detected by immunofluorescence towards TH (catecholaminergic), vesicular acetylcholine transporter (VAChT, cholinergic), and vasoactive intestinal peptide (VIP, cholinergic). Co-culture experiments with sympathetic ganglia and osteoclast progenitors or lymphocytes were performed to investigate stimulators of catecholaminergic-to-cholinergic transition.
Results: In mouse joint area, an increased ratio of density of cholinergic to catecholaminergic nerve fibers appeared towards day 35 after immunization. Most nerve fibers were located in joint-adjacent skin or muscle, and almost none were detected in inflamed synovial tissue or bony erosions. In human tissue samples from the knee and from interphalangeal joints, cholinergic, VAChT positive fibers are more present in OA synovial tissue than in RA. No difference in cholinergic, VIP positive nerve fiber density was found in these samples. Co-culture experiments of sympathetic ganglia from newborn mice with osteoclast progenitors obtained from healthy but not from arthritic animals induced catecholaminergic-to-cholinergic sympathetic transition. Leukemia inhibitory factor (LIF), a known transition factor from the glycoprotein 130 cytokine family, is present in low concentrations in supernatants from osteoclast progenitor cells but did not induce transition.
Conclusion: In men and mice, catecholaminergic-to-cholinergic sympathetic transition happens in less inflamed tissue but not in highly inflamed arthritic tissue. Under healthy conditions, presence of cholinergic sympathetic nerve fibers may support the cholinergic anti-inflammatory pathway recently described.
