Depression of stimulated arachidonate metabolism and superoxide production in rat alveolar macrophages following in vivo exposure to 0.5 PPM NO2

Abstract

Alveolar macrophages (AM) have been found to suffer significant functional deficits in response to nitrogen dioxide (NO₂) exposure. The present investigation examined changes in the activation of AM arachidonate metabolism and superoxide production in response to an environmentally relevant level of NO₂. Rats were exposed to 0.5 ppm NO₂ for periods of 0.5–10 d and AM were obtained by bronchoalveolar lavage (BAL). NO₂ exposure produced complex effects upon both unstimulated and stimulated AM arachidonate metabolism. Unstimulated AM synthesis of leukotriene B₄ (ITB₄) was depressed rapidly within 1 d of exposure, and depressed again at 5 d. Alveolar macrophage production of thromboxane B₂ (TxB₂), LTB₄, and 5‐hydroxyeicosatetraenoate (5‐HETE) in response to stimulation with the calcium ionophore, A23187, were acutely depressed within 1 d of exposure; however, generation of these compounds recovered to air‐control levels with longer exposure, while 5‐HETE was increased at 10 d. In contrast, AM production of LTB₄ in response to another stimulus, zymosan‐activated rat serum (ZAS), was not depressed until following 5 d of exposure and remained slightly lower than air‐control levels at 10 d. Levels of T_XB₂, LTB₄ prostaglandin E₂ (PGE₂), and prostaglandin F_2α (PCF_2α) measured in BAL fluid (BALF) were found to be depressed within 4 h of exposure, suggesting an acute decrease in the in vivo pulmonary arachidonate metabolism; however, production of these compounds generally recovered to air‐control levels with longer exposure. The AM superoxide production stimulated by phorbol myristate acetate (PMA) was decreased rapidly and continuously throughout the study. Thus, exposure to a low concentration of NO₂ acutely depresses activation of AM arachidonate metabolism and superoxide production in response to external stimuli, and may impede defense against pulmonary infection.