Modulation of ADP-stimulated inositol phosphate metabolism in rat alveolar macrophages by oxidative stress.

The present study examined alterations of adenosine-5-diphosphate (ADP)-stimulated inositol phosphate (IP3) metabolism and the respiratory burst of rat alveolar macrophages (AM) under oxidant stress using the model oxidant, tert-butyl hydroperoxide (tBOOH). Isolated AM were maintained in a system with an air-liquid interface, which approximates the lung environment. tBOOH produced a dual effect on the ADP-stimulated respiratory burst of these AM. Pretreatment of these AM with 50 microM tBOOH for 15 min led to a significant enhancement of the respiratory burst while significant inhibition was observed with 200 microM tBOOH. Treatment of AM with 100 microM ADP led to a significant increase in the generation of IP3, reaching a maximum at 30 s. In contrast, treatment of AM with 50 or 200 microM tBOOH did not stimulate IP3 generation during a 15-min period. Pretreatment of AM with 50 microM tBOOH for 15 min had no effect on ADP-stimulated IP3 generation. Preincubation with 200 microM tBOOH significantly inhibited generation of IP3 in response to ADP stimulation; however, this probably did not contribute to inhibition of the respiratory burst. The results suggest that production of IP3 may participate in stimulation of the respiratory burst by ADP but that enhancement of the respiratory burst by 50 microM tBOOH probably did not involve alteration of IP3 production.