Phospholipid turnover during phagocytosis in human polymorphonuclear leucocytes

Area of Science:

• Cellular Biology
• Immunology
• Biochemistry

Background:

• Phagocytosis of complement-coated zymosan by human polymorphonuclear leucocytes (PMNs) previously showed inhibited phosphatidylcholine synthesis via transmethylation.
• The specific pathways regulating phospholipid synthesis during phagocytosis require further elucidation.

Purpose of the Study:

• To investigate the effect of phagocytosis on phosphatidylcholine synthesis through the cholinephosphotransferase pathway.
• To determine the source of arachidonic acid generated during phagocytosis and its role in the process.

Main Methods:

• Measuring [Me-(14)C]choline incorporation into phosphatidylcholine in PMNs.
• Assaying CDP-choline:diacylglycerol cholinephosphotransferase activity.
• Analyzing arachidonic acid generation and phosphatidylinositol turnover.

Main Results:

• Phagocytosis significantly enhanced phosphatidylcholine synthesis via cholinephosphotransferase (up to 3-fold).
• Arachidonic acid generation primarily derived from phosphatidylinositol, mediated partly by phospholipase C.
• Inhibitors of phosphatidylinositol turnover reduced both arachidonic acid generation and phagocytosis.

Conclusions:

• Phagocytosis stimulates phosphatidylcholine synthesis through a pathway distinct from transmethylation.
• Phosphatidylinositol turnover plays a critical role in arachidonic acid release and is essential for phagocytosis by PMNs.