Regulation of human natural killing. I. The role of monocytes, interferon, and prostaglandins.
We have found that human endogenous natural killer activity as measured in a rapid 51Cr release assay is unaffected by the presence of monocytes. Moreover, stimulation of natural killer cells by poly I:C is independent of monocytes. In contrast, the presence of monocytes in a mixed population of mononuclear cells that have been stimulated by poly I:C suppresses NK activity. The suppression is shown to be partially reversible if indomethacin (10(-6) M) is added to the cultures during stimulation. Culture supernatants of monocytes stimulated with poly I:C are shown to contain PGE1 in a radioimmunoassay, and have NK inhibitory activity comparable to that obtained with exogenous PGE1 added to NK assays at a concentration range of 10(-7) to 10(-9) M. Culture supernatants from poly I:C-stimulated monocytes do not have detectable levels of antiviral activity. In contrast, plastic nonadherent cells stimulated with poly I:C produce significant levels of interferon (100 to 200 U/ml/2 x 10(6) cells) but almost undetectable amounts of PGE. Supernatants of nonadherent cells incubated with indomethacin (10(-6) M) alone augment NK activity. Taken together, the results suggest that stimulation of mononuclear cells with poly I:C is dependent on and regulated by the relative levels of interferon produced by lymphocytes and PGE produced by monocytes.
D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007372:Interferons / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D011453:Prostaglandins / Q000276:immunology*; D011458:Prostaglandins E / Q000494:pharmacology
D011453:Prostaglandins; D011458:Prostaglandins E; D007372:Interferons; D011070:Poly I-C; D007213:Indomethacin