Prostaglandin D(2) in Inflammatory Arthritis and Its Relation with Synovial Fluid Dendritic Cells

Prostaglandin (PG)D(2) has been shown to be an active agent in the resolution of experimentally induced inflammation. This study was undertaken to determine the presence of PGD(2) in chronic joint effusions and to explore the potential contributions of dendritic cells (DC) and monocytes to the intra-articular synthesis of PGD(2). Synovial fluid (SF) was obtained from patients with inflammatory arthritis and knee effusions. PGD(2) and PGE(2) were detected in SF by ultrahigh-performance tandem mass spectrometry. Cellular fractions in SF were separated by density-gradient centrifugation and flow cytometry. The expression of hematopoietic prostaglandin D-synthase (hPGDS) and PGE-synthase (PGES) mRNA was determined by RT-PCR. Both PGD(2) and PGE(2) were detected in blood and SF, with PGD(2) being more abundant than PGE(2) in SF. mRNA for hPGDS was more abundant in SF mDCs than SF monocytes (P < 0.01) or PB monocytes (P < 0.001). SF mDC expressed significantly more hPGDS than PGES. Expressions of PGD(2) and hPGDS were inversely associated with serum C-reactive protein (P < 0.01) and erythrocyte sedimentation rate (P < 0.01). The findings suggest that synovial DCs may be an important source of hPGDS and that systemic disease activity may be influenced by actions of PGD(2) in RA and other arthropathies.