TRANSCELLULAR REGULATION OF CELL RESPIRATION BY NITRIC-OXIDE GENERATED BY ACTIVATED MACROPHAGES

A macrophage cell line (J774), activated with interferon-gamma and end otoxin to express the inducible form of NO synthase (iNOS), immediatel y inhibited the cellular respiration of co-incubated L-929 fibroblasts or non-activated J774 macrophages, The inhibition was potent, rapid a nd reversible when the NO was removed by adding oxyhaemoglobin or by i nhibiting iNOS. Exogenously added NO also rapidly and reversibly inhib ited cellular respiration over the same range of NO concentrations. Th is inhibition was competitive with oxygen and due to direct inhibition of cytochrome oxidase. Thus, NO generated by one cell can regulate th e respiration of adjacent cells, supporting the hypothesis that NO may be a physiological and/or pathological regulator of cellular respirat ion, via its inhibition of cytochrome oxidase. (C) 1998 Federation of European Biochemical Societies.