Role of enhanced inositol phospholipid metabolism in neutrophil activation.
When guinea pig neutrophils were stimulated with chemotactic peptide [formylmethionyl-leucyl-phenylalanine (fMLP)], a marked release of lysosomal enzyme and production of superoxide anion were detected. The breakdown of phosphatidylinositol 4,5-bisphosphate (TPI) and the subsequent formation of diacylglycerol, phosphatidic acid and free arachidonic acid also occurred during the processes. Ca2+ ionophore A23187 caused an evident secretion of lysosomal enzyme but no superoxide anion production. Ca2+ ionophore also caused TPI breakdown to diacylglycerol although this breakdown was not as significant as that detected by fMLP. The tumor promotor tetradecanoylphorbol acetate (TPA), which is a strong activator of superoxide anion production but not a good stimulator of lysosomal enzyme secretion, did not cause a significant decrease of TPI or arachidonic acid release. Since TPA is known not to increase the intracellular Ca2+ level, these results suggest that lysosomal enzyme secretion is correlated closely with enhanced inositol phospholipid metabolism and Ca2+-dependent processes. On the other hand, superoxide anion production seemed to be caused mainly by Ca2+-independent processes, perhaps by protein kinase-C activation through newly formed diacylglycerol, when neutrophils were activated by chemotactic peptide.
Takenawa
T
T
Ishitoya
J
J
Homma
Y
Y
Kato
M
M
Nagai
Y
Y
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D006168:Guinea Pigs; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000097:blood*; D010766:Phosphorylation; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D001798:Blood Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D013481:Superoxides; D016718:Arachidonic Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium