CHRONIC BILIARY OBSTRUCTION INDUCES PULMONARY INTRAVASCULAR PHAGOCYTOSIS AND ENDOTOXIN SENSITIVITY IN RATS
CHRONIC BILIARY OBSTRUCTION INDUCES PULMONARY INTRAVASCULAR PHAGOCYTOSIS AND ENDOTOXIN SENSITIVITY IN RATS
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DOI：
10.1172/jci117554
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发表时间：
1994-11-01
影响因子：
15.9
通讯作者：
OHARA, N
中科院分区：
文献类型：
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作者：
CHANG, SW;OHARA, N
内毒素敏感性在不同动物种属之间存在差异，并且似乎与肺血管内巨噬细胞（PIM）的存在相关。在缺乏PIM的大鼠中，我们研究了慢性胆汁淤积性肝损伤导致PIM和内毒素敏感性诱导的假设。将大鼠随机分为胆总管结扎（BDL）组和假手术组，并在手术后1周（急性胆汁淤积）、2周（胆汁淤积，早期肝硬化）和4周（胆汁淤积，建立肝硬化）进行研究。血管内注射的荧光乳胶微球（1 μ m直径）被BDL大鼠肺实质中的大吞噬细胞吸收（在2和4周），而对照大鼠肺中未观察到吸收。电子显微镜检查显示肺毛细血管内含有摄入的乳胶颗粒的大单核巨噬细胞样细胞蓄积。肺血管内吞噬作用，反映在肺对Tc-99 m微聚集白蛋白的吸收中（微晶石，平均粒径= 1 μ m），平均0.7+/-0.1% 13只对照大鼠的总注射剂量（平均值+/-SEM），并在BDL后随时间逐渐增加（1周，1.71 ± 0.2%; 2周，10.0 ± 3.0%; 4周35.1 ± 5.9%）。胆汁性肝硬化大鼠对低剂量内毒素的致死作用明显敏感，并在死亡时表现出明显的肺水肿。此外，肺摄取血管内的I-125-脂多糖增加了五倍，在哮喘大鼠。我们的结论是，慢性胆道梗阻导致诱导肺血管内吞噬细胞和增强内毒素敏感性的大鼠。晚期肝硬化患者的肺血管内吞噬作用可能是他们对脓毒症诱导的成人呼吸窘迫综合征易感性增加的原因。
Endotoxin sensitivity varies among animal species and appears to correlate with the presence of pulmonary intravascular macrophage( PIM). In rats, which lack PIM, we investigated the hypothesis that chronic cholestatic liver injury leads to induction of PIM and endotoxin sensitivity. Rats were randomized to either common bile duct ligation (BDL) or sham-surgery and studied at 1 wk (acute cholestasis), 2 wk (cholestasis, early cirrhosis), and 4 wk (cholestasis, established cirrhosis) after surgery. Intravascularly injected fluorescent latex microspheres(1 mu m diameter) were taken up by large phagocytic cells in lung parenchyma of BDL rats (at 2 and 4 wk), while no uptake was observed in lungs from control rats. Electronmicroscopy revealed accumulation of large, mononuclear, macrophage-like cells containing ingested latex particles within the pulmonary capillaries. Pulmonary intravascular phagocytosis, as reflected in lung uptake of Tc-99m microaggregated albumin (Microlite, mean particle diameter = 1 mu m), averaged 0.7+/-0.1% (mean+/-SEM) of total injected dose in 13 control rats and progressively increased with time after BDL (1 wk, 1.71+/-0.2%; 2 wk, 10.0+/-3.0%; 4 wk 35.1+/-5.9%). Rats with biliary cirrhosis were markedly sensitive to the lethal effects of low dose endotoxin and demonstrated marked lung edema at the time of death. Furthermore, the lung uptake of intravascular I-125-lipopolysaccharide was increased fivefold in cirrhotic rats. We conclude that chronic biliary obstruction leads to the induction of pulmonary intravascular phagocytes and enhances endotoxin sensitivity in rats. Pulmonary intravascular phagocytosis in patients with advanced cirrhosis may account for their increased susceptibility to sepsis-induced adult respiratory distress syndrome.