Activation and inactivation of cyclo-oxygenase in rat alveolar macrophagesby aqueous cigarette tar extracts

Cyclo-oxygenase (COX) activity and its level of expression, the release of arachidonic acid (AA), and the accumulation of prostaglandins (PGs) were de termined in isolated rat pulmonary alveolar macrophages (PAM) exposed to aq ueous cigarette tar (ACT) extracts. COX activity increased 3-fold above the initial activity within 2 h of incubation with ACT extracts and gradually decreased below the initial activity after 8 h of incubation. The increased COX activity after 2 h of incubation did not lead to increased accumulatio n of PGE,. Accumulated levels of PGE, increased dramatically after 12 h of incubation despite decreased COX activity in cells incubated with ACT extra cts. This increased accumulation of PGE, was greater in cells derived from vitamin E deficient rats compared with control rats. Release of AA from cel ls was dramatically increased in cells incubated with ACT extracts in paral lel to PG accumulation. Thus increased accumulation of PGE, despite decreas ed COX activity after 12 h of incubation is likely the result of increased substrate availability. These results suggest that, contrary to earlier rep orts, cigarette smoke stimulates the formation of PGs in alveolar macrophag es. Increased PG production may lead to suppressed immune response and enha nced risk of tumorigenesis in smokers' lungs. (C) 1999 Elsevier Science Inc .