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  • Title: Uptake of fatty acids and their mobilization from phospholipids in cultured monocyte-macrophages from rheumatoid arthritis patients.
    Author: Bomalaski JS, Goldstein CS, Dailey AT, Douglas SD, Zurier RB.
    Journal: Clin Immunol Immunopathol; 1986 May; 39(2):198-212. PubMed ID: 2870830.
    Abstract:
    Prostaglandins (PG) and related eicosanoids which derive from essential fatty acids are important mediators and modulators of inflammation. Macrophages (M phi), 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 PGE2. 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-M phi). We examined uptake by M-M phi of eicosanoid precursor fatty acids (FA), their incorporation into cellular phospholipid (PL), and mobilization of FA after cell stimulation. Cultured M-M phi from treated and untreated RA patients (RA M-M phi) took up significantly more linoleic acid (LA), dihomogammalinolenic acid (DHLA) and arachidonic acid (AA) than M-M phi from normal volunteers (N M-M phi). The enhanced uptake of FA observed in 12-day cultures of RA M-M phi was similar to uptake seen in normal human peritoneal macrophages (PM phi). After uptake FA were incorporated mainly into phosphatidylcholine (PC). M-M phi 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-M phi with calcium ionophore A23187 resulted in significantly greater hydrolysis of LA and AA from PC in RA M-M phi from both treated and untreated patients than from PC in N M-M phi. The data indicate that M-M phi from RA patients mature more rapidly in vitro than M-M phi from controls as uptake of FA by RA M-M phi increases with duration of culture and by 12 days in culture equals uptake by normal human peritoneal M phi. Also, RA M-M phi exhibit differences from N M-M phi 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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