Cell specific synovial expression of nicotinic alpha 7 acetylcholine receptor in rheumatoid arthritis and psoriatic arthritis.
Neuroimmune interactions are known to influence several chronic inflammatory and rheumatic diseases, but the underlying mechanisms have been insufficiently elucidated. The cholinergic anti-inflammatory pathway is characterized by neural regulation of systemic inflammation, mediated by the vagus nerve and specific cholinergic stimulation of the nicotinic alpha-7 acetylcholine receptor (alpha7nAChR) on immune cells. Moreover, alpha7nAChR has been shown important for immune regulation also in the absence of nerves, but little is known about these mechanisms in chronic joint inflammation. The expression and localization of alpha7nAChR in synovial biopsies from patients with rheumatoid arthritis and psoriatic arthritis was investigated by immunohistochemistry using monoclonal antibody against alpha7nAChR. Surface staining of alpha7nAChR was observed in synovial tissue of all arthritis patients investigated and could also to a lesser extent be detected in the synovium of healthy individuals. alpha7nAChR positive cells were detected in mainly synovial lining cells and vessels. The alpha7nAChR positively stained cells were by double immunofluorescence identified as primarily macrophages and fibroblasts, with the majority of these cells expressing the receptor. These results indicate the importance of alpha7nAChR and cholinergic mechanisms in arthritis pathogenesis and implicate specific cholinergic modulation as a potential anti-inflammatory therapeutic strategy in joint inflammation.
Westman
M
M
Unit of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden. marie.westman@ki.se
Engström
M
M
Catrina
A I
AI
Lampa
J
J
D015535:Arthritis, Psoriatic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor