Mononuclear macrophages in pathogenesis of acute lung injury during acute obstructive cholangitis.

OBJECTIVE

To determine the role of mononuclear macrophages in the pathogenesis of acute lung injury during acute obstructive cholangitis.

METHODS

Sixty Wistar rats were used to study the correlation between the behavior of mononuclear macrophages and acute pulmonary injury during acute obstructive cholangitis (AOC). Animal model of AOC was made according to the method that the common bile duct was injected with Escherichia coli and ligated. The rats were killed at 6 h, 12 h, 24 h and 48 h after operation. The phagocytic function of Kupffer cells (KCs), the number of alveolar macrophages (AMs) in bronchoalveolar lavage liquid, and the extravascular water content of lung tissue were measured. The levels of lipid peroxide (LPO) and supperoxide dismutase (SOD) were determined too. Pathological alterations of liver and lung tissue were observed under light and electron microscopes.

RESULTS

KCs phagocytic function was significantly elevated at the 6th hour but markedly decreased from the 24th hour to the 48th hour in the AOC group as compared with the control (P<0.05). From the 12th to the 48th hour, the number of AMs, the extravascular water content of lung tissue, and the content of LPO significantly increased, but the SOD level of lung tissue decreased greatly (P<0.05). Morphologically, KCs proliferated diffusely in the early period in livers of the AOC group, but decreased markedly in the late period. Mitochondria of KCs were swollen or even vacuolated; focal cytoplasmic degeneration and many myeli like figures could be seen in the cytoplasm. The changes of injury such as disturbance of pulmonary capillary blood circulation, degeneration and/or necrosis of the lung tissue and endothelium, and inflammatory reactions could be observed. In other two groups, no evident morphological changes were observed.

CONCLUSIONS

KCs phagocytic function is decreased, whereas AM is activated by the invading bacteria to release such inflammatory mediators as free radicals, resulting in acute pulmonary injury. It seems that there is a close relationship between the functional status of mononuclear macrophages and the development of acute lung injury. The dysfunction of mononuclear macrophages may play an important role in the pathogenesis of multiple organ damage, especially acute pulmonary injury.