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Histaminergic Regulation of Natural Killer Cell‐Mediated Clearance of Tumour Cells in Mice
Author(s) -
ASEA A.,
HERMODSSON S.,
HELLSTRAND K.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1996.d01-14.x
Subject(s) - histamine , histaminergic , in vivo , histamine h2 receptor , biology , histamine h4 receptor , natural killer cell , monokine , pharmacology , receptor , endocrinology , immunology , chemistry , medicine , cytokine , in vitro , interleukin , antagonist , cytotoxicity , biochemistry , microbiology and biotechnology
Treatment of Swiss albino mice with histamine enhanced the clearance of natural killer (NK)‐cell sensitive YAC‐1 lymphoma and B16/F10 melanoma cells from lung tissue in vivo , but did not affect the elimination of NK‐cell‐insensitive P815mastocytoma cells. The effect of histamine was apparently mediated by H 2 ‐type histamine receptors (H 2 R) since it was blocked by ranitidine, an H 2 R antagonist. Histamine did not affect clearance of tumour cells in animalsdepleted of NK cells in vivo by treatment with antibodies to asialo‐GM1 or NK1.1. The effect of histamine was time‐dependent: pretreatment with histamine for 3 h significantly augmented the clearance of YAC‐1 cells, whereas, pretreatmentwith histamine for 5 min was ineffective. Histamine potentiated the anti‐tumour properties of NK‐cell activators such as interleukin‐2 (IL‐2) or interferon‐α (IFN‐α) in vivo . None of these lymphokines significantly affected theclearance of YAC‐1 cells unless animals were concomitantly treated with histamine. Treatment with ranitidine alone reduced the in vivo clearance of YAC‐1 cells from lungs but did not affect the clearance of NK‐cell‐insensitive P815 cells. Effects of ranitidine on NK‐cell function in vivo were not shared by a chemical control to ranitidine, AH20239AA, thus indicating that the inhibition of NK‐cells results from H 2 R antagonism rather than non‐specific toxicity. It is concludedthat histaminergic mechanisms may be involved in the regulation of NK cell function in vivo