Production of inositol-phospholipid-derived second messengers in a rat natural killer cell line exposed to susceptible tumor targets.
It is currently believed that natural killer (NK) cells kill bound target cells by exocytosis of cytotoxic granules via a calcium-dependent process. After confirming that NK-mediated killing was indeed dependent upon extracellular calcium, we investigated the production of inositol-phospholipid-derived second messengers in a rat NK cell line, RNK, upon exposure to susceptible target cells. These messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG), are associated with calcium-dependent secretory processes in a number of cell types. When RNK cells were exposed to susceptible YAC-1 tumor targets significant amounts of both IP3 and DAG were produced. The levels of the membrane phospholipid parent molecules of these second messengers declined in similarly stimulated RNK cells over a comparable time period. Using three different target cell lines, it was found that the levels of DAG that RNK produced in response to the different targets followed the same rank order as their susceptibility to RNK-mediated lysis. These data suggest that IP3 and DAG are produced in NK cells in response to tumor target cells, and these second messengers may have a functional role in NK-mediated killing.
Atkinson
E A
EA
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Gerrard
J M
JM
Hildes
G E
GE
Greenberg
A H
AH
D000818:Animals; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004075:Diglycerides / Q000096:biosynthesis* / Q000502:physiology; D005989:Glycerides; D007295:Inositol Phosphates / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D015290:Second Messenger Systems
D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D002118:Calcium