Inhibition of Lung Natural Killer Cell Activity by Smoking: The Role of Alveolar Macrophages

Abstract

Background: It is known that natural killer (NK) cell activity in the lung of smokers (SM) is lower than in non-smokers (NS). However, little is known about the underlying mechanisms. Objective: The purpose of this work was to investigate the mechanisms of the inhibition of NK cell activity by alveolar macrophages (AM) in SM. Methods: Lung effector cells and AM were obtained using bronchoalveolar lavage. The NK cell activity was assayed by ⁵¹Cr release method after incubation of 4 and 24 h, using K562 as target cell. AM were added at a concentration of 25% to effector cells. Results: Following 24-hour culture, NK cell activity significantly increased in the NS but not in the SM. Lung NK cell activity was significantly augmented by interleukin-2 in the NS but not in the SM. Addition of AM to the NK cell preparation from SM exerted a significantly greater suppressive effect on autologous blood NK cell activity than in the NS. Indomethacin, catalase or thiourea did not prevent AM-mediated suppression of NK cell activity, in contrast to superoxide dismutase. Conclusions: These results suggest that the suppression of NK cell activity by AM in SM may be caused by O^–₂ release rather than by prostaglandins, H₂O₂ or OH release from AM.

Alveolar Macrophage from Cigarette Smoke-Exposed Mice Inhibits B Lymphocyte Proliferation Stimulated with LPS

“…These findings suggest that the inhibition of AM-mediated LPS-induced B lymphocyte proliferation in CS-exposed mice is probably caused by excessive increased superoxide and hydrogen peroxide generations by cigarette smoking. We have previously reported that the AM-mediated inhibition of natural killer cell activity in cigarette smokers was prevented by SOD [8]. Therefore, excessive increased superoxide and hydrogen peroxide generations in AM from CS-exposed mice may lead to oxidant stress for pulmonary immune system and inhibit immune functions.…”

“…We previously reported that AM in cigarette smokers exerted significantly greater suppressive effect on autologous natural killer cell activity than AM in nonsmokers because of increased oxygen radical by CS [8]. In this study, we investigated whether there was a difference between CS-exposed and non-CS-exposed mice in the response of AM on lipopolysaccharide (LPS)-induced B lymphocyte proliferation.…”

Impact of smoking on outcome of resected lung adenocarcinoma

“…Second, smoking contributes to an increase in the white blood cell count and a decline in the circulating natural killer (NK) cell count [13]. Third, smoking has been reported to reduce local airway immunity and that the alveolar macrophages of smokers suppressed NK cell activity by producing prostaglandins and oxygen radicals [14]. Taken together, smoking not only causes lung cancer but it also might negatively affect the prognosis of patients with lung adenocarcinoma.…”

Cigarette Smoke Induce Alteration of Structure and Function in Alveolar Macrophages

“…6). It has previously been reported that CS increased reactive oxygen species (ROS) generation in AM [11], [12]. CS-induced DNA damage may cause by excess of ROS production.…”