Phospholipase A2s constitute a wide group of
lipid -modifying
enzymes which display a variety of functions in
innate immune responses . In this
work , we utilized
mass spectrometry -based
lipidomic approaches to investigate the action of
Asp -49 Ca2+-dependent
secreted phospholipase A2 (
sPLA2 ) (
MT-III ) and Lys-49
sPLA2 (MT-II), two group IIA
phospholipase A2s isolated from the
venom of the
snake Bothrops asper , on
human peripheral
blood monocytes .
MT-III is catalytically active, whereas MT-II lacks
enzyme activity. A large decrease in the
fatty acid content of
membrane phospholipids was detected in
MT III -treated
monocytes . The significant diminution of the cellular content of
phospholipid -bound
arachidonic acid seemed to be mediated, in part, by the activation of the endogenous group IVA cytosolic
phospholipase A2a.
MT-III triggered the formation of
triacylglycerol and
cholesterol enriched in palmitic, stearic, and
oleic acids , but not
arachidonic acid , along with an increase in
lipid droplet synthesis. Additionally, it was shown that the increased availability of
arachidonic acid arising from
phospholipid hydrolysis promoted abundant
eicosanoid synthesis. The inactive form, MT-II, failed to produce any of the effects described above. These studies provide a complete
lipidomic characterization of the
monocyte response to
snake venom group IIA phospholipase A2 , and reveal significant connections among
lipid droplet biogenesis,
cell signaling and biochemical pathways that contribute to initiating the inflammatory response.