Phospholipid turnover during phagocytosis in human polymorphonuclear leucocytes.
We have previously observed that the phagocytosis of zymosan particles coated with complement by human polymorphonuclear leucocytes is accompanied by a time- and dose-dependent inhibition of phosphatidylcholine synthesis by transmethylation [García Gil, Alonso, Sánchez Crespo & Mato (1981) Biochem. Biophys. Res. Commun.101, 740-748]. The present studies show that phosphatidylcholine synthesis by a cholinephosphotransferase reaction is enhanced, up to 3-fold, during phagocytosis by polymorphonuclear cells. This effect was tested by both measuring the incorporation of radioactivity into phosphatidylcholine in cells labelled with [Me-(14)C]choline, and by assaying the activity of CDP-choline:diacylglycerol cholinephosphotransferase. The time course of CDP-choline:diacylglycerol cholinephosphotransferase activation by zymosan mirrors the inhibition of phospholipid methyltransferase activity previously reported. The extent of incorporation of radioactivity into phosphatidylcholine induced by various doses of zymosan correlates with the physiological response of the cells to this stimulus. This effect was specific for phosphatidylcholine, and phosphatidyl-ethanolamine turnover was not affected by zymosan. The purpose of this enhanced phosphatidylcholine synthesis is not to provide phospholipid molecules rich in arachidonic acid. The present studies show that about 80% of the arachidonic acid generated in response to zymosan derives from phosphatidylinositol. A transient accumulation of arachidonoyldiacylglycerol has also been observed, which indicates that a phospholipase C is responsible, at least in part, for the generation of arachidonic acid. Finally, isobutylmethylxanthine and quinacrine, inhibitors of phosphatidylinositol turnover, inhibit both arachidonic acid generation and phagocytosis, indicating a function for this pathway during this process.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D002798:Diacylglycerol Cholinephosphotransferase / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000097:blood; D010743:Phospholipids / Q000097:blood*; D011796:Quinacrine / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D016718:Arachidonic Acid; D015054:Zymosan; D002798:Diacylglycerol Cholinephosphotransferase; D011796:Quinacrine; D015056:1-Methyl-3-isobutylxanthine