IN-VITRO EFFECTS OF NITROGEN-DIOXIDE ON THE RELEASE OF SUPEROXIDE ANIONS, TNF-ALPHA, AND IL-8 BY HL-60-MACROPHAGES AND BOVINE ALVEOLAR MACROPHAGES

This study was designed to investigate the in vitro effect of nitrogen dioxide on some immunofunctions of immune-competent cells. HL60-cells, differentiated into macrophages with calcitriol (HL60-M), and bovine alveolar macrophages (BAM) were exposed to synthetic air or to NO2 (1.5 and 3.0 ppm) for 1 or 2 h. Under the special conditions of exposure, which allow the cells to be kept in direct contact with the gases during the whole incubation period, the cells stay alive in synthetic air for more than 4 h. After a lag phase of about 1 h, the exposure to NO2 results in a decrease of the viability, which is dependent both on the time and on the concentration. The morphology of the cell surface structures is obviously changed, even under conditions in which a loss of viability cannot yet be observed. Simultaneously, the capability of the cells to generate superoxide anions in response to a stimulation with zymosan, but not with TPA, is markedly reduced and, in addition, the spontaneous release of superoxide anions from nonstimulated cells is also diminished after their exposure to NO2. Like the superoxide anion production, the tumor necrosis factor alpha (TNF-alpha) and the interleukin 8 (IL-8) releases by both types of cell in response to a stimulation with lipopolysaccharide (LPS) are significantly suppressed after NO2 exposure. But whereas the exposure to NO2 increases the liberation of TNF-alpha and IL-8 by nonstimulated H160-M, the TNF-alpha release of resting BAMs is drastically suppressed. The results indicate that NO2 has some distinct effects on immunologically relevant functions of H160-M and BAMs. The effects concern mainly the capability of the cells to respond to external stimuli and only in a minor extent the functions of resting cells. These findings can help to explain the reported higher susceptibility to infections of animals that have been exposed to NO2.