IL-12 or IL-15, unlike IL-2, does not interact with histamine in augmenting cytotoxicity of splenocytes against melanoma cells and YAC-1 cells.
It has been suggested that histamine by its ability to downregulate the production of macrophage-derived reactive oxygen species might effectively potentiate the cytotoxic activity of cytokine-stimulated NK cells. Histamine thus reverses negative regulation of NK cells treated with IL-2 and IFN-alpha in the presence of macrophages. We confirm that histamine potently enhances cytotoxic activity of IL-2-stimulated NK cell-enriched splenocytes admixed with macrophages against B16F10 melanoma cells and YAC-1 cells. This stimulation results in production of high amounts of INF-gamma and TNF-alpha. Interestingly, IL-15 by itself promotes production of reactive oxygen species. Although histamine decreased reactive oxygen species production from the cultures of IL-15-stimulated NK cell-enriched splenocytes admixed with macrophages, it did not potentiate the cytotoxicity of IL-15. Further, we demonstrate that histamine-mediated potentiation of cytotoxicity is not applicable to IL-12, another potent activator of NK cell activity.
Kozar
Katarzyna
K
Department of Immunology, Center of Biostructure, 02-004 Warsaw, Poland.
Kaminski
Rafal
R
Giermasz
Adam
A
Basak
Grzegorz
G
Zagozdzon
Radoslaw
R
Rybczynska
Jolanta
J
Wasik
Maria
M
Lasek
Witold
W
Jakobisiak
Marek
M
Golab
Jakub
J
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010537:Peritoneum / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019409:Interleukin-15; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D006632:Histamine; D007371:Interferon-gamma