Activation and inactivation of cyclo-oxygenase in rat alveolar macrophages by aqueous cigarette tar extracts.
Activation and inactivation of cyclo-oxygenase in rat alveolar macrophages by aqueous cigarette tar extracts.
复制标题
水性香烟焦油提取物对大鼠肺泡巨噬细胞中环加氧酶的激活和灭活。
DOI：
10.1016/s0891-5849(99)00120-3
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发表时间：
1999
影响因子：
7.4
通讯作者：
Pryor,WA
中科院分区：
文献类型：
--
作者：
Hwang,D;Chanmugam,P;Boudreau,M;Sohn,KH;Stone,K;Pryor,WA
本实验观察了香烟焦油（ACT）提取物对离体大鼠肺泡巨噬细胞（PAM）环氧合酶（考克斯）活性及其表达水平、花生四烯酸（AA）释放和前列腺素（PGs）积累的影响。考克斯活性在与ACT提取物孵育2小时内增加3倍，高于初始活性，并在孵育8小时后逐渐降低至低于初始活性。孵育2 h后，增加的考克斯活性并不导致PGE 2积累增加。尽管ACT提取物孵育的细胞中考克斯活性降低，但孵育12 h后PGE 2的累积水平显著增加。与对照组大鼠相比，来自维生素E缺乏大鼠的细胞中PGE2的积累增加。与PG积累平行，ACT提取物孵育的细胞中AA从细胞中的释放显著增加。因此，尽管孵育12小时后考克斯活性降低，但PGE 2积累增加可能是底物可用性增加的结果。这些结果表明，与早期报道相反，香烟烟雾刺激肺泡巨噬细胞中PG的形成。PG产生增加可能导致免疫反应受到抑制，并增加吸烟者肺部肿瘤发生的风险。
Cyclo-oxygenase (COX) activity and its level of expression, the release of arachidonic acid (AA), and the accumulation of prostaglandins (PGs) were determined in isolated rat pulmonary alveolar macrophages (PAM) exposed to aqueous 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 accumulation of PGE2. Accumulated levels of PGE2increased dramatically after 12 h of incubation despite decreased COX activity in cells incubated with ACT extracts. This increased accumulation of PGE2was greater in cells derived from vitamin E deficient rats compared with control rats. Release of AA from cells was dramatically increased in cells incubated with ACT extracts in parallel to PG accumulation. Thus increased accumulation of PGE2despite decreased COX activity after 12 h of incubation is likely the result of increased substrate availability. These results suggest that, contrary to earlier reports, cigarette smoke stimulates the formation of PGs in alveolar macrophages. Increased PG production may lead to suppressed immune response and enhanced risk of tumorigenesis in smokers’ lungs.