Induction of cytosolic phospholipase A2 in human leukocytes by lipopolysaccharide.
Stimulation of peripheral blood leukocytes with lipopolysaccharide results in the synthesis of inflammatory cytokines including interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha and prostaglandin E2 correlating with an increase in phospholipase A2 activity. Mammalian cells contain several phospholipase A2 isoforms including the 14-kDa secretory isoform and the more recently described high-molecular-mass cytosolic isoform. It is commonly believed that during inflammatory responses secretory phospholipase A2 becomes activated. However, we could not detect secretory phospholipase A2 nor its corresponding mRNA after lipopolysaccharide-induced activation. By contrast, we found increased mRNA levels for cytosolic phospholipase A2 following activation of peripheral blood leukocytes when levels were compared to non-stimulated controls. Our results demonstrate that cytosolic phospholipase A2, rather than the secretory isoform may be the mediator of the lipopolysaccharide-induced inflammatory cascade in human peripheral blood leukocytes.
Rodewald
E
E
Boehringer Mannheim GmbH, Department of Immunology and Oncology, Penzberg, Germany.
Tibes
U
U
Maass
G
G
Scheuer
W
W
D001483:Base Sequence; D016207:Cytokines / Q000032:analysis*; D003600:Cytosol / Q000201:enzymology*; D015232:Dinoprostone / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007527:Isoenzymes / Q000096:biosynthesis; D007962:Leukocytes / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008233:Lymphotoxin-alpha / Q000032:analysis; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone