Inhibitory mechanisms of antibody production by nitrogen oxides released from activated macrophages during the immune response: relationship to energy consumption.
We investigated the relationship between the sensitivity of mouse splenocytes in immune response to nitrogen oxides and energy consumption rate of the cells. Macrophage-like cells (Mm1) pretreated with IL-6 served as the source of the nitrogen oxides. The antibody production of both 2,4,6-trinitrophenyl-keyhole limpet haemocyanin-primed splenocytes and B cell hybridomas was markedly reduced; about 20-40% of splenocytes and B cell hybridomas were killed by co-culture with IL-6-treated Mm1. Cell viability and antibody production were completely restored by the addition of NG-monomethyl L-arginine to the culture medium. The cytotoxicity of the nitrogen oxides was correlated with the distance between effector and target cells. Under conditions of low cytotoxicity, antibody production by B cell hybridomas was suppressed by the nitrogen oxides, this suppression not being correlated with the reduction in cell growth. The sensitivity of the target cells differed in co-cultures of antigen-primed splenocytes and B cell hybridomas with IL-6-treated Mm1. The nitric oxide-sensitivity of the cells corresponded to their 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reducing activity and ATP consumption rate. These findings suggest that nitrogen oxides act as regulatory molecules in immune response in three ways: cytostasis, reduction of cell growth and suppression of antibody synthesis.
Takagi
K
K
Department of Environmental Biochemistry, School of Pharmaceutical Science, University of Shizuoka, Japan.
Nukaya
I
I
Yasukawa
K
K
Suketa
Y
Y
D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004734:Energy Metabolism / Q000502:physiology*; D006825:Hybridomas / Q000276:immunology; D015850:Interleukin-6 / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009589:Nitrogen Oxides / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015850:Interleukin-6; D009589:Nitrogen Oxides