Effect of exposure to nitrogen dioxide on alveolar macrophage-mediated immunosuppressive activity in rats.

Nitrogen dioxide (NO2), a major component of air pollutants, induces inflammatory responses in the lungs. Resident alveolar macrophages (AM) play an immunosuppressive role in the lungs via suppression of lymphocyte proliferation, and nitric oxide (NO) plays a crucial role in this immunosuppressive activity. Microenvironmental changes within the alveoli during inflammatory responses, however, can inhibit this immunosuppressive activity of AM. The present study was designed to clarify the effect of NO2 exposure on the immunosuppressive activity of and NO production by AM in rats. Wistar rats were exposed to 10 ppm NO2 for 3, 14 or 28 days, after which bronchoalveolar lavage fluid (BALF) was taken as a sample of the alveolar microenvironment. Suppression of concanavalin A-induced lymphocyte proliferation and NO production by AM were markedly inhibited by BALF from NO2-exposed rats (NO2-BALF). The inhibitory effect of NO2-BALF at 28-days exposure was stronger than that of NO2-BALF at 3 or 14 days exposure. In conclusion, AM-mediated immunosuppressive activity was inhibited by the NO2-induced changes of the alveolar microenvironment through the inhibition of NO production.