Effect of cyclosporin A on the membrane-associated events in human leukocytes with special reference to the similarity with dexamethasone.
The effect of an immunosuppressive drug, cyclosporin A, and dexamethasone was assessed on the enzymatic reactions of membrane phospholipid in normal human lymphocytes and neutrophils. Incubation for 20 min with cyclosporin A markedly suppressed, in a dose dependent manner, phospholipase A2 activity and the release of prostaglandin E2 in lymphocytes, and slightly those in neutrophils, while no inhibition of phosphatidylethanolamine (PE)-N methyltransferase activity was observed. Choline phosphotransferase (CPT) activity was not inhibited by the drug, either. These inhibitory effects on enzyme activities of membrane phospholipid are similar to those of dexamethasone, although different incubation time of the drug was required to induce inhibitory effects. These findings suggest that cyclosporin A acts upon early membrane events in the activation of cells involved in inflammatory reactions; they further suggest that suppression of immune response by cyclosporin A is at least partly due to inhibition of phospholipase A2 in the plasma membrane of inflammatory cells. This inhibition reduces the production of cell membrane lyso-phosphatidylcholine (PC) and arachidonic acid from PC, which is produced by transmethylation of PE and cytidine diphosphate (CDP) choline pathway of which the last reaction to PC is mediated by CPT.
Niwa
Y
Y
Kano
T
T
Taniguchi
S
S
Miyachi
Y
Y
Sakane
T
T
D002462:Cell Membrane / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D008780:Methyltransferases / Q000097:blood; D009504:Neutrophils / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism
D003524:Cyclosporins; D008563:Membrane Lipids; D010743:Phospholipids; D011458:Prostaglandins E; D003907:Dexamethasone; D008780:Methyltransferases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone