Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients.
Open Access
- 1 October 1996
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 184 (4), 1519-1524
- https://doi.org/10.1084/jem.184.4.1519
Abstract
We have demonstrated spontaneous nitric oxide (NO) production by primary synovial cultures from rheumatoid (RA) and osteoarthritis patients. Increased NO production followed addition of staphylococcal enterotoxin B. Immunochemical double staining with specific anti-human inducible NO synthase (iNOS) and nonspecific esterase (NSE), or anti-CD68 (markers for tissue macrophages) showed that although many lining layer cells in RA synovium expressed iNOS, most (approximately 90%) were NSE- and CD68-, with only a minor population (approximately 10%) which were iNOS+, CD68+/NSE+. These data demonstrate the capacity for high output of NO by human synovial tissue and show that, although human macrophages can express high levels of iNOS, the majority of cells expressing iNOS are fibroblasts. We also report that synoviocytes, and macrophage cell lines, cultured with the NO donor, S-nitroso-acetyl penicillamine, produced high concentrations of tumor necrosis factor (TNF)-alpha. These results suggest that NO may mediate pathology in RA through the induction of TNF-alpha production.Keywords
This publication has 27 references indexed in Scilit:
- ROLE OF CYTOKINES IN RHEUMATOID ARTHRITISAnnual Review of Immunology, 1996
- The L-Arginine-Nitric Oxide PathwayNew England Journal of Medicine, 1993
- Modulation of human t cell responses by nitric oxide and its derivative, s‐nitrosoglutathioneArthritis & Rheumatism, 1993
- Suppression of arthritis by an inhibitor of nitric oxide synthase.The Journal of Experimental Medicine, 1993
- Nitric Oxide Synthase Is Not a Constituent of the Antimicrobial Armature of Human Mononuclear PhagocytesThe Journal of Infectious Diseases, 1993
- Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases.Annals Of The Rheumatic Diseases, 1992
- Transcriptional activation of IL-1 beta and tumor necrosis factor-alpha genes by MHC class II ligands.The Journal of Immunology, 1991
- The Staphylococcal Enterotoxins and Their RelativesScience, 1990
- INHIBITORY EFFECT OF TNF$alpha; ANTIBODIES ON SYNOVIAL CELL INTERLEUKIN-1 PRODUCTION IN RHEUMATOID ARTHRITISThe Lancet, 1989
- Nonspecific acid esterase activity: A criterion for differentation of T and B lymphocytes in mouse lymph nodesEuropean Journal of Immunology, 1975