Imipramine and chloroquine induced alterations in phospholipid content of rat lung

The influence of the amphiphilic drugs imipramine (150 mg/kg b. w./day) and chloroquine (75 mg/kg b. w./day) on the phospholipid (PL) -metabolism of rat lung, its PL-content and PL-composition were measured in the cell free lung lavage fluid (alveolar surfactant), in the free alveolar cells (mainly alveolar macrophages), and in the residual lung tissue. In addition to the long-term administration (15 applications during a period of 3 weeks), the influence of short-term administration (2 or 4 applications, resp., during a period of 2 or 4 days) was examined. The alveolar macrophages show the largest increase in PL-content. As revealed by its composition the stored PL are of surfactant origin. In chloroquine treated rats the number of macrophages is increased as well. The concentration of stored PL is higher in macrophages of imipramine treated rats. The excessive accumulation of PL in this animal group possibly impairs the clearance function of alveolar macrophages. This is suggested to be the reason for the accumulation of alveolar surfactant in imipramine treated rats. The influence of the drugs on the PL-content of the residual lung tissue was weak. The results of this study show that amphiphilic drugs cause an accumulation of surfactant-PL within the alveolar macrophages and can promote the alveolar surfactant content even after short-term application. The role of alveolar macrophages in alveolar surfactant catabolism is demonstrated.