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

为了阐明类二十烷酸、补体和内毒素在ARDS发病机制中的作用，我们采用败血性肺模型研究了盲肠结扎穿刺后大鼠AM的功能变化。A23187刺激败血性AM产生的白三烯B_4' 12-和5-HETEs明显少于对照AM。脓毒症大鼠支气管肺泡灌洗液中免疫反应性LTC_4高于对照组大鼠。因此，我们推测内毒素中毒大鼠的AM在肺泡中释放脂肪加氧酶代谢物，而这些AM所获得的5-1加氧酶活性降低。相反，这些细胞释放的O_2^-在PMA刺激的量增加。接下来，我们研究了静脉注射大肠杆菌LPS对注射后第1天和第3天肺泡（AM）和腹膜巨噬细胞（PM）超氧阴离子（O_2^-）产生和花生四烯酸5-脂氧合酶代谢的影响。所选择的剂量是在肺血管中发现可引起明显的I-BSA渗漏^<125>。注射lps 1天后获得的AM在C5a刺激下产生的O^-_量较少，但在小麦胚芽凝集素（WGA）或花生四烯酸（AA）刺激下产生的O^-_量与对照AM相同。这一结果表明补体的激活是预先的。相反，在第3天，三种刺激中的任何一种，它们的O^-_产量都显著超过对照AM。lps注射后第1天收集的PM在WGA或AA刺激下产生的O^-_量明显高于对照PM。然而，从第1天到第3天，O^-_的量减少了。LPS 1 d后收集的AM在A23187单独和AA联合刺激下产生的LTB_4和5-HETE明显高于未处理的大鼠细胞。这些活动在第3天收集的AM中恢复到控制水平。相比之下，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天的细胞产生的LTB_4明显更多。巨噬细胞注射LPS后，5-1氧合酶和O -_生成系统的不同反应和时间过程可能表明两种生成系统的调节机制存在差异。AM较PM早期增加内源性AA利用率，可诱导二次刺激后产生更多的LTB_4，从而吸引更多的白细胞到肺中。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