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，我们采用大鼠盲肠结扎穿孔后脓毒肺模型，研究了AM功能的变化。脓毒症AM经A23187刺激后产生的白三烯B_4、12-和5-HETE明显少于对照AM。脓毒症组大鼠支气管肺泡灌洗液中LTC_4免疫反应阳性率明显高于对照组。因此，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，使肺泡巨噬细胞5- 1脂氧合酶活性降低。相反，这些细胞在PMA刺激下释放出更多的O_2^-。在注射后第1和第3天，观察了LPS对肺泡巨噬细胞（AM）和腹腔巨噬细胞（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。的 关于我们 与<125>对照AM相比，注射LPS后1天获得的AM在C5 a刺激下产生的O^-_量较低，但在小麦胚芽凝集素（WGA）或花生四烯酸（AA）刺激下产生的O^-_量相同。该结果表明存在既往补体激活。相反，在第3天，它们产生的O^-_显著超过了对照AM。注射LPS后第1天收集的PM在WGA或AA刺激下产生的O^-_显著高于对照PM。LPS刺激后第1天收集的AM细胞经A23187单独刺激和与AA联合刺激后，其LTB_4和5-HETE的生成量均显著高于对照组。在第3天收集的AM中，这些活动恢复到对照水平。而第1天收集的PM产生的LTB_4和5-HETE与对照PM相似，而第3天收集的PM产生的LTB_4显著高于对照PM。5- 1脂氧合酶和O^-_产生系统的不同反应和时程可能表明LPS诱导的巨噬细胞对这两种产生系统的调节机制不同。AM较PM内源性AA利用率的早期增加，可诱导第二次刺激后更多的LTB_4产生，从而使更多的白细胞被吸引到肺内。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