Production of PAF-acether by synovial fluid neutrophils in rheumatoid arthritis
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PAF-acether (PAF) is a pro-inflammatory phospholipid molecule potentially involved in the pathogenesis of arthritis. PAF and related metabolites have been isolated in the synovial fluid from patients with arthritis.
The aim of this study was to determine PAF production by neutrophils isolated from synovial fluid and blood in patients with rheumatoid arthritis. Blood neutrophils from normal donors were also studied for their capacity to form PAF. Neutrophils were stimulated with the calcium ionophore A23187 (2µM) for 1 to 60min. PAF released in the medium and PAF associated to cells were measured.
In synovial fluid neutrophils, PAF production began as soon as 1 min of stimulation (16.1 ± 6.3 pmol per 1 × 106 cells) and reached a maximum at 20min: 29.2 ± 2.8 pmol per 1 × 106 cells (mean ± SEM, n = 5). The amount of PAF released in the supernatant increased with the length of stimulation and was maximal after 30min (33.5%, percentage of released over total PAF, n = 5). After A23187 stimulation, similar amounts of PAF were produced by blood neutrophils from RA and control patients. However, neutrophils isolated from the joint had a lower capacity to produce PAF than blood neutrophils from the same patients.
The present results demonstrate the synthesis and release of PAF by synovial fluid neutrophils. They suggest that neutrophils may be the source of PAF locally present in the joint. Newly synthetised PAF could participate in the amplification of the local inflammatory reaction.
Key wordsPlatelet-activating factor Neutrophils Rheumatoid arthritis Synovial fluid
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