Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells

Delayed parenchymal phase images of the liver more than 5 min after IV injection of ultrasound contrast agents are thought to be related to the phagocytosis of contrast agent microbubbles by macrophages. In this study, we examined whether liver-specific macrophages, Kupffer cells, phagocytosed the microbubbles and whether their elimination affected the delayed parenchymal images of the liver. Phase-contrast microscope observations showed that Kupffer cells phagocytosed various contrast agents in vitro. Among the contrast agents used, 99% of Sonazoid™ and Optison™, and 47% of Levovist™ were phagocytosed, whereas only 7.3% of SonoVue™ and 0% of Imavist™ were phagocytosed. Elimination of Kupffer cells in vivo by gadolinium chloride (GdCl3) resulted in decreased intensity of the delayed parenchymal images with Sonazoid™ and Levovist™, while SonoVue™ showed no changes compared with control. Our findings suggested that Kupffer cells phagocytosed contrast agents and they were responsible for the delayed images of contrast ultrasound in the liver. (E-mail: moriyasu@tokyo-med.ac.jp)