Immunoglobulin G-mediated phagocytosis activates a calcium-independent, phosphatidylethanolamine-specific phospholipase.
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 Fc gamma 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 < or = 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-(1-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 receptor-activated, calcium-independent phospholipase from human monocytes.
Lennartz
M R
MR
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Lefkowith
J B
JB
Bromley
F A
FA
Brown
E J
EJ
D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000378:metabolism / Q000502:physiology*; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology; D010587:Phagocytosis / Q000502:physiology*; D010714:Phosphatidylethanolamines / Q000378:metabolism / Q000502:physiology*; D010740:Phospholipases / Q000032:analysis / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011753:Pyrones / Q000494:pharmacology; D017452:Receptors, IgG / Q000032:analysis / Q000378:metabolism / Q000502:physiology
D001095:Arachidonic Acids; D007074:Immunoglobulin G; D009281:Naphthalenes; D010714:Phosphatidylethanolamines; D011753:Pyrones; D017452:Receptors, IgG; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D010740:Phospholipases; D010741:Phospholipases A; D002118:Calcium