CD16 cross-linking induces both secretory and extracellular signal-regulated kinase (ERK)-dependent cytosolic phospholipase A2 (PLA2) activity in human natural killer cells: involvement of ERK, but not PLA2, in CD16-triggered granule exocytosis.
The phospholipase A2 (PLA2) enzymes play a central role in diverse cellular processes including phospholipid digestion and metabolism, host defense, and cell signaling. We investigated the ability of CD16 clustering to trigger PLA2 and extracellular signal-regulated kinase (ERK) activation in human NK cells, as well as their possible involvement in CD16-stimulated degranulation. Both secretory (sPLA2) and cytosolic (cPLA2) PLA2 were rapidly activated upon CD16 cross-linking; sPLA2 was found in the supernatant and also in a cell-associated form. cPLA2 activation was controlled by the ERK pathway as indicated by the close correlation between their kinetics of activation and by the ability of the specific MEK inhibitor, PD 098059, to abolish cPLA2 activation. CD16 stimulation also resulted in the generation of platelet-activating factor (PAF) and leukotrienes; both phospholipases contributed to their biosynthesis. Using the pharmacologic inhibitors AACOCF3, p-bromophenacyl bromide (pBPB), and PD 098059, which specifically inhibit cPLA2, sPLA2, and MEK, respectively, we demonstrated that the ERK signaling pathway, but not cytosolic or secretory PLA2, is required for CD16-triggered granule release.
Milella
M
M
Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Italy.
Gismondi
A
A
Roncaioli
P
P
Bisogno
L
L
Palmieri
G
G
Frati
L
L
Cifone
M G
MG
Santoni
A
A
D000911:Antibodies, Monoclonal / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000276:immunology; D003600:Cytosol / Q000201:enzymology*; D004789:Enzyme Activation / Q000276:immunology; D004790:Enzyme Induction / Q000276:immunology; D005089:Exocytosis / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000378:metabolism; D010741:Phospholipases A / Q000096:biosynthesis* / Q000502:physiology; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D010972:Platelet Activating Factor; D017452:Receptors, IgG; D016718:Arachidonic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2