A histochemical study of the rheumatoid synovium: focus on nitric oxide, nerve growth factor high affinity receptor, and innervation.
OBJECTIVE
The synovium of patients with rheumatoid arthritis (RA) is characterized by massive cell proliferation, neoangiogenesis, and apoptosis. The nature of potential repressors/inducers of these phenomena is still largely unknown. We investigate if nitric oxide (NO) and nerve growth factor (NGF) can be considered potential mediators in these phenomena in RA.


METHODS
Synovium of 15 patients with RA in active phase and synovium of 14 patients without synovial inflammation were processed for histochemical (NADPH-diaphorase) and immunohistochemical visualization of different isoforms for the NO synthesis enzyme NO synthase (NOS) and for NGF high affinity receptor trkA.


RESULTS
Inducible NOS (iNOS) immunoreactivity and NADPH-diaphorase positivity were found in synoviocytes, fibroblast-like synoviocytes, fibroblasts, and inflammatory cells in the rheumatoid synovium. In the same areas and in the same cell types, although not in the same cells, we also found positivity for the NGF high affinity receptor trkA.


CONCLUSIONS
We suggest that all elements involved in the transduction pathway that is activated by NGF and that proceeds through NO and tumor suppressor p53 are present in the synovium during RA, controlling cell cycle arrest, cell differentiation, and apoptosis.
Pozza
M
M
Pathophysiology Center for the Nervous System, Hesperia Hospital, Modena, Italy.
Guerra
M
M
Manzini
E
E
Calza
L
L
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D020932:Nerve Growth Factor / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis*; D020917:Receptor, trkA / Q000032:analysis*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000737:chemistry / Q000201:enzymology / Q000294:innervation / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D020932:Nerve Growth Factor; D020917:Receptor, trkA