Chronic Biliary Obstruction Induces Pulmonary Intravascular Phagocytosis and Endotoxin Sensitivity in Rats

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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 microns 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 Technetium-99m microaggregated albumin (Microlite, mean particle diameter = 1 microns), averaged 0.7 +/-0.1% (mean +/-SEM) of total injected dose in 13 control rats and progressively increased with time after BDL (1 wk, 1.7 +/-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 Iodine-125-lipopolysaccharide was increased five-fold 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. (J. Clin. Invest. 1994. 94:2009-2019.) Key words: liver cirrhosis. bile duct ligation. pulmonary intravascular macrophage. sepsis. lung injury

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