D. Hwang et al., Activation and inactivation of cyclo-oxygenase in rat alveolar macrophagesby aqueous cigarette tar extracts, FREE RAD B, 27(5-6), 1999, pp. 673-682
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
.