Proliferation of mononuclear phagocytes (Kupffer cells) and endothelial cells in regenerating rat liver. A light and electron microscopic cytochemical study.

Abstract

The proliferation of littoral cells in regenerating rat liver after partial hepatectomy has been investigated using endogenous peroxidase and uptake of large (0.8-mu) latex particles as markers of Kupffer cells. Female rats were subjected to 2/3 partial hepatectomy and sacrificed at intervals up to 11 days. Prior to sacrifice, animals were injected with latex and their livers were fixed by perfusion and were processed for cytochemical localization of peroxidase. The sinusoidal cells exhibited a marked regenerative response after partial hepatectomy. Peroxidase activity persisted in endoplasmic reticulum of Kupffer cells during mitosis. Furthermore, latex particles were exclusively localized in such peroxidase-positive cells, thus confirming their identity as Kupffer cells. Quantitative counts revealed that the peak mitotic activity of Kupffer cells occurred at 48 hours, whereas that of endothelial cells was at 96 hours after partial hepatectomy. Our findings indicate that Kupffer cells are capable of dividing locally in the liver; no morphologic evidence of transformation of endothelial cells or monocytes to Kupffer cells was found. The significance of these observations concerning the origin of Kupffer cells is discussed, and it is concluded that in the model of liver regeneration after partial hepatectomy the Kupffer cells are formed predominantly by local cell division.