Analysis for roles of complement and arachidonate metabolites in occurrence and progression of ARDS.

为了阐明二十烷类化合物、补体和内毒素在ARDS发病机制中的作用，我们利用大鼠盲肠结扎和穿孔术后脓毒症肺模型，研究了AM的功能变化。A23187刺激败血症AM产生的白三烯B_4、‘12-和5-HETE明显少于对照AM。脓毒症大鼠支气管肺泡灌洗液中LTC_4免疫反应阳性细胞明显多于对照组。推测内毒素血症大鼠肺泡巨噬细胞释放脂氧合酶代谢产物，使5-1环氧合酶活性降低。相比之下，这些细胞在PMA刺激下释放的O2^-增加。接下来，我们研究了静脉注射的影响。分别于注射后第1天和第3天，观察细菌脂多糖对小鼠肺泡巨噬细胞(AM)和巨噬细胞(PM)超氧阴离子(O2^-)和花生四烯酸5-脂氧合酶代谢的影响。The…与对照组相比，注射内毒素后一天获得的AM对C5a刺激产生的O^-_on量较少，而与小麦胚凝集素(WGA)或花生四烯酸(AA)产生的量相同这一结果表明补体被激活了。相反，在第3天，它们产生的O^-_显著高于三种刺激中的任何一种的对照AM。注射内毒素后第1天采集的PM在WGA或AA刺激下产生的O^-_on刺激量显著高于对照PM注射内毒素后第1天至第3天，A23187单独刺激和与AA联合刺激产生的LTB_4和5-HETE显著高于未处理的大鼠。相反，第1天收集的PM产生的LTB_4和5-HETE的量与对照PM相似，但第3天收集的细胞产生的LTB_4明显多于对照组。5-1环氧合酶和O^-生成系统的不同反应和时间进程可能表明，注射内毒素后巨噬细胞中这两种产生系统的调节机制有所不同。本研究还提示，AM较PM早期内源性AA可利用性增加，可在二次刺激后产生更多的LTB_4，从而可能吸引更多的白细胞进入肺。较少

To elucidate roles of eicosanoids, complement, and endotoxins in pathogenesis of ARDS, we studied functional changes of AM by using a septic lung model of rats after the operation of cecal ligation and puncture. Septic AM generated significantly less amounts of leukotriene B_4' 12- and 5-HETEs by stimulation with A23187 than the control AM did. Immunoreactive LTC_4 in the bronchoalveolar lavage fluids from the septic rats was more than that from the control rats. Therefore, it was speculated that the AM of endotoxemic rats released lipoxygenase metabolites in alveoli and then these AM obtained showed reduced 5-1ipoxygenase activity. In contrast, these cells released enhanced amounts of O_2^- on stimulation with PMA.Next, we studied influences of the i.v. administration of E. coli LPS on the production of superoxide anion (O_2^-) and 5-lipoxygenase metabolism of arachidonic acid were evaluated in the alveolar (AM) and peritoneal macrophages (PM) on days 1 and 3 after the injection. The … More dose selected was that found to induce a significant leakage of ^<125> I-BSA in the pulmonary vasculature.AM obtained one day after the LPS-injection generated smaller amount of O^-_ on stimulation with C5a but generated same amounts with wheat germ lectin (WGA) or arachidonic acid (AA) compared to control AM. This result suggested a prior complement activation. On day 3, on the contrary, their production of O^-_ significantly exceeded that by the control AM with either of the three stimuli. PM collected on day 1 after the LPS-injection generated a significantly greater amount of O^-_ on stimulation with either WGA or AA than did control PM. The amount of O^-_, however, decreased from day 1 to day 3.AM collected one day after the injection of LPS generated significantly more LTB_4 and 5-HETE on stimulation with A23187 alone and in combination with AA than did the cells from untreated rats. Such activities returned to the control levels in the AM collected on day 3. In contrast, the PM collected on day 1 produced amounts of LTB_4 and 5-HETE similar to those of the control PM but the cells on day 3 produced significantly more LTB_4.Differing responses and time-courses in 5-1ipoxygenase and O^-_ generation system may indicate a difference in mechanisms that regulate the two production systems in macrophages following the injection of LPS. It is also suggested that early increase of endogenous AA availability in AM compared with PM induces more production of LTB_4 following second stimulation and consequently more leukocytes may be attracted to the lung. Less