Abstract
Prostaglandins (PG) and related eicosanoids which derive from essential fatty acids are important mediators and modulators of inflammation. Macrophages (Mϕ), which derive from peripheral blood monocytes (PBM), are prominent cells in the synovium of patients with rheumatoid arthritis (RA), and are a major source of synovial PGE 2. In addition, fresh and cultured PBM from RA patients produce more PG than normal control cells. When allowed to mature in culture PBM exhibit many characteristics of macrophages (M-Mϕ). We examined uptake by M-Mϕ of eicosanoid precursor fatty acids (FA), their incorporation into cellular phospholipid (PL), and mobilization of FA after cell stimulation. Cultured M-Mϕ from treated and untreated RA patients (RA M-Mϕ) took up significantly more linoleic acid (LA), dihomogammalinolenic acid (DHLA) and arachidonic acid (AA) than M-Mϕ from normal volunteers (N M-Mϕ). The enhanced uptake of FA observed in 12-day cultures of RA M-Mϕ was similar to uptake seen in normal human peritoneal macrophages (PMϕ). After uptake FA were incorporated mainly into phosphatidylcholine (PC). M-Mϕ from untreated RA patients incorporated a smaller proportion of [ 14C]LA into PC (37.0 ± 12.7% of total PL label) than normal cells (86.0 ± 4.2%), and a greater proportion of [ 3H]AA into PC (57.1 ± 7.1%) than normals (23.9 ± 6.9%). Stimulation of M-Mϕ with calcium ionophore A23187 resulted in significantly greater hydrolysis of LA and AA from PC in RA M-Mϕ from both treated and untreated patients than from PC in N M-Mϕ. The data indicate that M-Mϕ from RA patients mature more rapidly in vitro than M-Mϕ from controls as uptake of FA by RA M-Mϕ increases with duration of culture and by 12 days in culture equals uptake by normal human peritoneal Mϕ. Also, RA M-Mϕ exhibit differences from N M-Mϕ in uptake, PL distribution, and hydrolysis of eicosanoid precursor FA. Such changes in FA metabolism might influence cell function and inflammatory responses.
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