Evidence for Kupffer cell migration along liver sinusoids, from high-resolution in vivo microscopy

Abstract

Kupffer cells are generally considered fixed tissue macrophages of the liver. However, we have evidence that this opinion is incorrect. High-resolution in vivo video microscopy shows that Kupffer cells have the ability to migrate along sinusoidal walls. Images recorded from anesthetized mice show active locomotion of cells with or against the direction of blood flow or in the absence of flow. The size, changing morphology, and uptake of carbon or microspheres strongly suggest that these are Kupffer cells. Quantitative measurements were made on 29 migrating Kupffer cells. The mean speed of migration was 4.6 +/- 2.6 (SD) microns/min and was not significantly different whether migration occurred with or against the flow. When fluorescent microspheres were given in vivo as a phagocytic challenge, Kupffer cells containing few microspheres migrated more slowly (0.9 +/- 0.9 microns/min, n = 10), whereas those containing many microspheres were never seen to migrate. Individual Kupffer cells were able to move independently, i.e., in directions different from those of neighboring Kupffer cells. These findings may have major implications for the role of Kupffer cells in scavenging foreign particles and as antigen-presenting cells.