Phospholipase A2-Mediated Fusion of Neutrophil-Derived Membranes Is Augmented by Phosphatidic Acid

• Published in: Biochemical and biophysical research communications Vol. 282; no. 2; pp. 480 - 486
• Main Authors: Harsh, Donna M., Blackwood, R.Alexander
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 30-03-2001
• Subjects: arachidonic acid; membrane fusion; phosphatidic acid; phospholipase A2; phospholipase D; arachidonic acid; phospholipase D; phosphatidic acid; phospholipase A2; membrane fusion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.4601

Phosphatidic acid (PA), the product of phospholipase D (PLD) metabolism, is not only an important second messenger in neutrophil signal transduction but PA generation increases membrane fusogenicity. Following neutrophil stimulation, PA formation can be detected in azurophil, specific, and plasma membrane vesicle subcellular fractions, suggesting a potential role for PA formation in granule–plasma membrane fusion. Neutrophil stimulation also activates phospholipase A2 (PLA2) and the release of arachidonic acid. In vitro fusion of plasma membrane vesicles and specific granules with complex liposomes were dependent on PLA2 (<10 μM Ca2+) while the presence of PA in the liposomes augmented the effects of PLA2. Azurophil granules were extremely resistant to fusion (no fusion at 12 mM Ca2+ even in the presence of PLA2). However, in the presence of both PA and PLA2 fusion could be detected at <5 μM Ca2+, suggesting a direct role for phospholipid metabolism in neutrophil degranulation.