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 b urst of rat alveolar macrophages (AM) under oxidant stress using the m odel oxidant, tert-butyl hydroperoxide (tBOOH), Isolated AM were maint ained 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 mu M t BOOH for 15 min led to a significant enhancement of the respiratory bu rst while significant inhibition was observed with 200 mu M tBOOH, Tre atment of AM with 100 mu M ADP led to a significant increase in the ge neration of IP3, reaching a maximum at 30 s, In contrast, treatment of AM with 50 or 200 mu M tBOOH did not stimulate IP3 generation during a 15-min period. Pretreatment of AM with 50 mu M tBOOH for 1.5 min had no effect on ADP-stimulated IP3 generation. Preincubation with 200 mu M tBOOH significantly inhibited generation of IP3 in response to ADP stimulation; however, this probably did not contribute to inhibition o f the respiratory burst, The results suggest that production of IP3 ma y participate in stimulation of the respiratory burst by ADP but that enhancement of the respiratory burst by 50 mu M tBOOH probably did not involve alteration of IP3 production. (C) 1995 Academic Press,Inc.