Signal transduction pathways leading to arachidonic acid release from neutrophilic HL-60 cells. The involvement of G protein, protein kinase C and phospholipase A2.
Arachidonic acid release from undifferentiated and neutrophilic HL-60 cells was studied. In neutrophilic cells it was stimulated by N-formyl-Met-Leu-Phe and mastoparan by a mechanism involving Gi protein and phospholipase C and was largely dependent on diacyglycerol lipase. Maximum release from both cell types was achieved with fluoride and required cellular energy. Inhibitor studies suggest that arachidonic acid release by fluoride stimulation leads to phospholipase A2 activation with signal transduction involving phospholipase C and protein kinase C. Only neutrophilic cells responded to phorbol ester if Ca(2+)-ionophore was simultaneously present but this effect was abolished by extended treatment with phorbol ester. Thus, protein kinase C plays a major role in highly stimulated neutrophilic cells. These cells are differently equipped with protein kinase C isoenzymes compared with undifferentiated cells. In contrast, both cell types contain similar levels of type II and cytosolic phospholipases A2, the former being by far the more prevalent.
Institut für Biologische Chemie, Universität Heidelberg, Germany.
W J
WJ
Buhl
B
B
Yu
U
U
Gehring
D016718:Arachidonic Acid / Q000378:metabolism*; D002454:Cell Differentiation; D004591:Electrophoresis, Polyacrylamide Gel; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D018922:HL-60 Cells / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D014862:Wasp Venoms / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; C037500:mastoparan; D011493:Protein Kinase C; D010741:Phospholipases A; D008071:Lipoprotein Lipase; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D005459:Fluorides