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Synovial fluid polymorphonuclear leucocytes from patients with rheumatoid arthritis have reduced MPO and
E V Davies1, B D Williams, A K Campbell
1Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff.
Abstract:
Synovial fluid (SF) polymorphonuclear leucocytes (PMN) from patients with rheumatoid arthritis (RA) were compared to RA and normal circulating blood PMN. RA SF PMN were as viable as blood PMN and remained viable for up to 24 h in culture. Measurement of myeloperoxidase indicated that RA SF PMN had degranulated and secreted their myeloperoxidase prior to isolation, 26.5 +/- 11.7% being found extracellularly compared to less than 2.9% in RA and normal blood PMN. RA SF PMN alone showed a decrease in basal NADPH-oxidase activity as well as an increase in responsiveness to stimulation by chemotactic peptide during culture. Stimulation of PMN with phorbol-12-myrisitate-13-acetate evoked equivalent responses in each population before and after culture. These results demonstrate a major difference in resting and receptor-mediated activation of superoxide release by RA SF PMN. Together, these results have important implications in identifying the role of the activated PMN in RA.
Insights
Rheumatoid arthritis (RA) synovial fluid polymorphonuclear leucocytes (PMN) show distinct degranulation and altered superoxide release compared to blood PMN. These findings highlight the activated PMN
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation.
- Polymorphonuclear leucocytes (PMN) are key immune cells implicated in inflammatory processes.
- Understanding PMN behavior in the synovial fluid (SF) of RA patients is crucial for elucidating disease pathogenesis.
Purpose of the Study:
- To compare the characteristics and functional responses of PMN isolated from RA synovial fluid with those from RA and normal blood.
- To investigate the activation status and superoxide release capabilities of RA SF PMN.
Main Methods:
- Isolation and culture of PMN from RA synovial fluid and peripheral blood.
- Assessment of PMN viability and myeloperoxidase (MPO) extracellular levels.
- Measurement of NADPH-oxidase activity under basal and stimulated conditions (chemotactic peptide, phorbol-12-myristate-13-acetate).
Main Results:
- RA SF PMN exhibited significant prior degranulation, with higher extracellular MPO levels compared to blood PMN.
- RA SF PMN showed reduced basal NADPH-oxidase activity but enhanced responsiveness to chemotactic peptide stimulation during culture.
- Superoxide release stimulated by phorbol-12-myristate-13-acetate was comparable across all PMN populations before and after culture.
Conclusions:
- RA SF PMN display unique functional differences in resting and receptor-mediated activation of superoxide release compared to blood PMN.
- These distinct properties of activated PMN in the RA joint have significant implications for understanding RA pathogenesis.
- The findings suggest a critical role for activated PMN in the inflammatory cascade of rheumatoid arthritis.