Phospholipases and phagocytosis: the role of phospholipid-derived second messengers in phagocytosis (original) (raw)
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Phospholipase A2IV Regulates Phagocytosis Independent of Its Enzymatic Activity
Journal of Biological Chemistry, 2012
Background: The mechanistic regulation of phagocytosis by phospholipase A 2 (PLA 2) remains to be defined. Results: A specific PLA 2 isoform is activated during phagocytosis, translocates to the plasma membrane, and directly participates in phagosome formation, without involving its enzymatic activity. Conclusion: PLA 2 IV␣ regulates phagocytosis via a novel mechanism that requires membrane binding of its C2 domain. Significance: PLA 2 IV␣ mediates a novel mechanism of phagocytosis regulation.
The Journal of Cell Biology, 1996
Phosphoinositide 3-kinase (PI 3-kinase) has been implicated in growth factor signal transduction and vesicular membrane traffic. It is thought to mediate the earliest steps leading from ligation of cell surface receptors to increased cell surface ruffling. We show here that inhibitors of PI 3-kinase inhibit endocytosis in macrophages, not by interfering with the initiation of the process but rather by preventing its completion. Consistent with earlier studies, the inhibitors wortmannin and LY294002 inhibited fluid-phase pinocytosis and Fc receptor-mediated phagocytosis, but they had little effect on the receptor-mediated endocytosis of diI-labeled, acetylated, low density lipoprotein. Large solute probes of endocytosis reported greater inhibition by wortmannin than smaller probes did, indicating that macropinocytosis was affected more than micropinocytosis. Since macropinocytosis and phagocytosis are actin-mediated processes, we expected that their inhibition by wortmannin resulted ...
Phospholipid Turnover During Phagocytosis In Human Polymorphonuclear Leucocytes
Biochemical …, 1982
We have previously observed that the phagocytosis of zymosan particles coated with complement by human polymorphonuclear leucocytes is accompanied by a timeand dose-dependent inhibition of phosphatidylcholine synthesis by transmethylation [Garcia Gil, Alonso, Sanchez Crespo & Mato (1981) Biochem. Biophys. Res. Commun. 101, 740-7481. 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-'4C]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 phosphatidylethanolamine 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.
Journal of Leukocyte Biology, 1993
Inhibition of arachidonate release down- regulates immunoglobulin G-mediated phagocytosis. This arachidonate requirement is selective for IgG- opsonized targets, suggesting that arachidonate may act as a second messenger for Fcγ receptor-mediated phagocytosis. Here we report the characterization of a phospholipase, activated during phagocytosis, that releases arachidonate from phosphatidylethanolamine in the absence of intracellular calcium ([Ca]i ≤ 2 nM). In vitro, a phospholipase with these characteristics was detected in soluble and particulate fractions of human monocyte homogenates. (E)-6-(Bromomethylene)tetrahydro-3-(l- naphthalenyl)-2H-pyran-2-one, a drug that selectively inhibits Ca-independent phospholipase A2S, is shown to inhibit IgG-mediated phagocytosis and its associated arachidonate release in intact monocytes as well as the in vitro enzyme activity. These findings provide a link between the whole-cell and in vitro data and present the initial characterization of a re...
Signaling and membrane dynamics during phagocytosis: many roads lead to the phagos(R)ome
Current Opinion in Cell Biology, 2004
Phagocytosis is the mechanism used by specialized cells such as macrophages, dendritic cells and neutrophils to internalize, degrade and eventually present peptides derived from particulate antigens. This process relies on profound rearrangements of the actin cytoskeleton and the plasma membrane to engulf particles. Recent work has highlighted the early recruitment of internal membranes derived from endocytic compartments and from the endoplasmic reticulum to allow plasma membrane extension at the onset of phagocytosis. This ensures that the phagosome is rapidly provided with the machinery appropriate for later phagocytic functions, including particle degradation and antigen presentation. Abbreviations ARF ADP ribosylation factor CR complement receptor ER endoplasmic reticulum FcR Fc receptor GEF guanine nucleotide exchange factor Ig immunoglobulin ITAM immunoreceptor tyrosine-based activation motif MHC major histocompatibility complex PH domain pleckstrin homology domain PI3K phosphatidylinositol 3 0 -kinase PI3P phosphatidylinositol 3-phosphate PIP2 phosphatidylinositol 4,5-bisphosphate PIP3 phosphatidylinositol 3,4,5-trisphosphate PIPKIa phosphatidylinositol-4-phosphate 5-kinase Ia RNAi RNA interference SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptors TAP transporter associated with antigen processing VAMP vesicle-associated membrane protein WASP Wiscott-Aldrich syndrome protein
Phosphoinositides and phagocytosis
The Journal of Cell Biology, 2001
Phosphoinositide 3 kinases (PI3Ks)* are known as regulators of phagocytosis. Recent results demonstrate that class I and III PI3Ks act consecutively in phagosome formation and maturation, and that their respective products, phosphatidylinositol 3,4,5-trisphosphate (PI[3,4,5]P 3 ) and phosphatidylinositol 3-phosphate (PI[3]P), accumulate transiently at different stages. Phagosomes containing Mycobacterium tuberculosis do not acquire the PI(3)Pbinding protein EEA1, which is required for phagosome maturation. This suggests a possible mechanism of how this microorganism evades degradation in phagolysosomes.
Journal of Cell Science, 1997
Arachidonic acid is essential for antibody-mediated phagocytosis but its role in this process has not been defined. The phospholipase A2 inhibitor bromoenol lactone decreases arachidonic acid release and arrests phagocytosis; this effect is bypassed by the addition of arachidonic acid to bromoenol lactone-treated cells. In this morphological study, monocytes treated with bromoenol lactone accumulate electronlucent vesicles in the cytoplasm underlying bound targets. The vesicles are not contiguous with the plasma membrane as they are not labeled with cationized ferritin and are not connected to the plasma membrane as determined by high voltage electron microscopy imaging. However, if the plasma membrane is decorated with wheat germ agglutinin-gold prior to vesicle formation, virtually all vesicles contain the gold marker, indicating that they are plasma membrane-derived. The number of vesicles decreases dramatically upon addition of arachidonic acid to phospholipase A2-inhibited mono...