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Impaired interleukin-8-dependent chemotaxis by synovial fluid polymorphonuclear leukocytes in rheumatoid arthritis
H Hashimoto1, M Yamamura, K Nishiya
1Third Department of Internal Medicine, Okayama University Medical School, Japan.
Abstract:
The accumulation of polymorphonuclear leukocytes (PMN) in synovial fluid is a common feature of rheumatoid arthritis (RA). We studied the chemotactic response of PMN obtained from the synovial fluid and from the peripheral blood of patients with RA using a modified Boyden's method, in which interleukin-8 (IL-8) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used as a chemotactic agent. The IL-8-induced response of peripheral blood PMN from 15 patients with RA did not differ from that of 15 healthy controls. A decreased chemotactic response to IL-8 was, however, observed in PMN from the synovial fluid of 12 patients with RA compared with peripheral blood cells of the same individual. This defective chemotactic ability of PMN was inversely correlated with the number of infiltrating cells in the synovial fluid. We also obtained similar results with FMLP. These results indicate that the chemotactic ability of PMN may be reduced after migrating to the synovial fluid.
Insights
Polymorphonuclear leukocytes (PMN) in rheumatoid arthritis (RA) synovial fluid show reduced chemotaxis. This impaired cell migration to inflammation sites suggests a defect acquired after entering the joint fluid.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMN) accumulate in synovial fluid during rheumatoid arthritis (RA).
- The function of these cells within the joint is crucial for understanding RA pathogenesis.
Purpose of the Study:
- To investigate the chemotactic response of PMN from rheumatoid arthritis patients' synovial fluid compared to peripheral blood.
- To determine if IL-8 and FMLP induce differential responses in PMN based on their location (synovial fluid vs. peripheral blood).
Main Methods:
- Utilized a modified Boyden's method to assess PMN chemotaxis.
- Employed interleukin-8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) as chemotactic agents.
- Compared chemotactic responses of synovial fluid PMN and peripheral blood PMN from the same RA patients.
Main Results:
- Peripheral blood PMN from RA patients showed normal chemotactic response to IL-8 compared to healthy controls.
- PMN from RA synovial fluid exhibited a significantly decreased chemotactic response to IL-8 and FMLP compared to their peripheral blood counterparts.
- The reduced chemotactic ability of synovial fluid PMN was inversely correlated with the number of infiltrating cells in the synovial fluid.
Conclusions:
- PMN chemotactic function is impaired after migration into the synovial fluid of RA patients.
- This defect may influence the inflammatory process and cell infiltration dynamics in rheumatoid arthritis.
- Synovial fluid environment may induce functional changes in PMN relevant to RA pathology.