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 char acterized by massive cell proliferation, neoangiogenesis, and apoptosis. Th e nature of potential repressors/inducers of these phenomena is still large ly unknown. We investigate if nitric oxide (NO) and nerve growth factor (NG F) 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 (N ADPH-diaphorase) and immunohistochemical visualization of different isoform s for the NO synthesis enzyme NO synthase (NOS) and for NGF high affinity r eceptor trkA. Results. Inducible NOS (iNOS) immunoreactivity and NADPH-diaphorase positiv ity 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 positiv ity for the NGF high affinity receptor trkA. Conclusion. We suggest that all elements involved in the transduction pathw ay that is activated by NGF and that proceeds through NO and tumor suppress or p53 are present in the synovium during RA, controlling cell cycle arrest , cell differentiation, and apoptosis.