title: Phosphatidylinositol metabolism accompanies early activation events in tumor target cell-stimulated human natural killer cells.
abstract: This study examined the role of phospholipid metabolism in human natural killer (NK) cells upon activation by tumor target cells(TC). The effector cell (EC) population consisted of peripheral blood lymphocytes enriched for NK cells. Upon a 5-min exposure of EC to the NK-sensitive tumor TC K562 and U937, nearly four- and threefold increases in the incorporation of 32P into phosphatidylinositol (PI) occurred, respectively. In contrast, no increase in 32P incorporation into PI was seen when two NK-resistant TC were used. In addition, little or no change in the incorporation of 32P into phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine took place with any of the above TC. Depletion of Leu 11b-positive cells abolished the increase in 32P incorporation into PI when K562 were used in the phospholipid assay. Furthermore, labeling kinetics of this phospholipid turnover showed that it occurred less than 5 min following exposure to NK-sensitive TC and that phosphatidic acid, a breakdown product of phosphoinositides, was produced during this 5-min period. These results indicated that metabolism of a phosphoinositide took place and that it occurred in association with early activation events in NK cells. Quercetin and dibutyryladenosine-cyclic monophosphate (dbcAMP) plus theophylline exerted profound inhibitory effects on both NK activity and PI metabolism, suggesting a linkage between the two events. The inhibitors had no effect on target cell-binding capacity, indicating that the inhibition occurred postbinding. PI metabolism took place in the absence of extracellular calcium even though NK activity was completely abolished under the same conditions. Thus, we have shown PI metabolism, but not other phospholipids, to occur in human NK cells upon exposure to NK-sensitive TC, in association with early activation events. This event was independent of extracellular calcium and could be inhibited by quercetin or dbcAMP plus theophylline.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46223.
authors.forename: T A
authors.initials: TA
authors.lastname: Steele
authors.forename: Z
authors.initials: Z
authors.lastname: Brahmi
mesh_terms: D000328:Adult; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
chemical_list: D010716:Phosphatidylinositols; D003994:Bucladesine; D011794:Quercetin; D013806:Theophylline; D002118:Calcium