Premium
Inhibitory mechanisms of antibody production by nitrogen oxides released from activated macrophages during the immune response: Relationship to energy consumption
Author(s) -
TAKAGI KUNIAKI,
NUKAYA IKUEI,
YASUKAWA KIYOSHI,
SUKETA YASUNOBU
Publication year - 1994
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1994.36
Subject(s) - splenocyte , cytostasis , immune system , nitric oxide , antibody , chemistry , microbiology and biotechnology , cytotoxicity , cell culture , biology , biochemistry , immunology , in vitro , genetics , organic chemistry
Summary 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 (Mm 1) pretreated with lL‐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 Mm 1. Cell viability and antibody production were completely restored by the addition of N G ‐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 Mm 1. 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.