Prostaglandin E2 receptor activity and susceptibility to natural killer cells.
We have described a high-affinity receptor for prostaglandin E2 (PGE2) present on metastatic murine mammary tumor cells. Pharmacologic antagonism of this receptor increases metastatic potential. In the present study, we have asked whether the binding activity of PGE on tumor target cells plays a role in natural killer (NK)-target cell interactions. We have used three unrelated PGE-receptor antagonists, SC19220, LEO101, and AH6809, to show inhibition of [3H]PGE2 binding to YAC-1 cells and inhibition of PGE2-mediated elevation of intracellular cyclic AMP (cAMP). Addition of any of these three receptor antagonists to standard 4-h 51Cr-release assays inhibits YAC-1 lysis by NK-enriched populations from murine spleen. This is the first report that antagonism of PGE binding affects NK activity. Our studies demonstrate that these effects are mediated through inhibition of target-effector cell conjugate formation. Studies in which effector and target cells were pretreated separately indicate that the PGE-mediated effects are expressed at the target cell level.
Fulton
A M
AM
University of Maryland Cancer Center, Baltimore.
Chong
Y C
YC
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011121:Polyphloretin Phosphate / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018078:Receptors, Prostaglandin E
D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D011121:Polyphloretin Phosphate; D000242:Cyclic AMP; D007213:Indomethacin