Enhanced phospholipase activity in peripheral blood monocytes from patients with rheumatoid arthritis.
Peripheral blood monocytes (PBM) from patients with rheumatoid arthritis (RA) produce greater amounts of prostaglandins (PG) than do control cells. To further explore the reasons for the increased PG production, we assessed the phospholipase activities in these cells. We found that PBM from patients with severe RA expressed greater phospholipase A2 (PLA2) and phospholipase C (PLC) activities than did the control cells. Enhanced PLA2 activities were observed in RA patient cells when phosphatidylcholine (PC) or phosphatidylethanolamine (PE) were used as substrates. Enhanced PLC activities also were seen when PC, PE, and phosphatidylinositol (PI) were used as labeled substrates. Increased PLC activity was observed whether linoleic acid or arachidonic acid was esterified to the 2 position of the phospholipid substrate used. Because all patients with RA were treated with nonsteroidal antiinflammatory drugs, we examined the effects of aspirin ingestion on phospholipase activities. Aspirin had no consistent effect on PLA2 activities but markedly inhibited PLC activities against PC, PI, and PE with arachidonic acid in the R2 position. That aspirin enhanced PLC activities against PC and PI with linoleic acid in the R2 position, suggests that PLC activity may be regulated in part by the R2 fatty acid. Our results indicate that increased phospholipase activities exhibited by PBM from RA patients may help explain the increased PG production by these cells. The increased phospholipase activities in PBM from RA patients do not appear to be due solely to nonsteroidal antiinflammatory drug therapy.
D001172:Arthritis, Rheumatoid / Q000097:blood*; D006801:Humans; D008264:Macrophages / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology*; D010586:Phagocytes / Q000201:enzymology; D010740:Phospholipases / Q000097:blood*; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D010738:Type C Phospholipases / Q000097:blood*
D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases