Emperipolesis of erythroblasts within Kupffer cells during hepatic hemopoiesis in human fetus

Abstract

The state in which cells can inhabit other cells without damage is known as emperipolesis. Emperipolesis has been found in various physiological and pathological conditions. We performed a study of emperipolesis of erythroblasts within Kupffer cells in the human fetal liver. We found that Kupffer cells, identified by CD68 immunolabeling, contained 4-8 erythroblasts in a hypertrophic cytoplasm on light microscopy. Emperipoletic erythroblasts were present in various maturation stages from proerythroblast to reticulocyte. By electron microscopy, we found that erythroblasts occupied membrane-bound vacuoles that were separated from each other by thin partitions of Kupffer cell cytoplasm. Neither emperipoletic erythroblasts nor their Kupffer cell hosts showed evidence of damage. Emperipoletic cells in mitosis were found, which suggests the capacity for the proliferation of erythroblasts within Kupffer cells. Some Kupffer cells were seen to contain both emperipoletic cells and phagosomes, without evidence of interaction. Erythroblasts and other hemopoietic cells were also found to be closely associated with the sinusoidal surface of Kupffer cells. However, intercellular junctions, if present, were inconspicuous. On occasion, Kupffer cells engorged with erythroblasts nearly occluded the sinusoidal lumen. Our results demonstrate that emperipolesis of erythroblasts within Kupffer cells occurs in human fetal hepatic hemopoiesis. We suggest that emperipolesis may be one of the mechanisms that support the maturation of erythroblasts in the fetal liver.

Modeling cell-in-cell structure into its biological significance

“…Similar observation is reported that liver epithelial cells act as nursing cells to promote the maturation of erythrocytes 26 or eliminate auto-reactive immune cells through negative selection to maintain homeostasis. 27 Benseler et al 27 recently found that most naive autoreactive T cells, being adoptively transferred into recipient animals, concentrated in the liver and were internalized into epithelial cells.…”

Biological relevance of cell-in-cell in cancers

“…The term cannibalism has also been used to describe melanoma tumour cells engulfing immune cells [2,24]. The more widely used term for tumour cells engulfing immune cells is emperipolesis, although this term has also been used for other non-tumourous CIC structures, including oligodendrocytes residing in astrocytes or erythrocytes residing in Kupffer cells [25–28]. Tumour cell-associated emperipolesis has mainly been studied in histological sections with limited mechanistic details.…”

Emperipolesis, entosis and cell cannibalism: Demystifying the cloud

“…The emperipoletic activity of erythroblasts in liver has been found to increase in periods of high level of hepatic erythropoietic activity and relatively anemic fetal state. [13]…”

“…Emperipolesis is now understood as a mechanism to improve cell survival and help prevent apoptosis of cells within the host cell or control cells that could be cytotoxic to the host cells. [13]…”

“…[13] No such obvious cell-to-cell binding and/or communication has been noted in the occurrence of emperipolesis of erythroblasts by Kupffer cells in fetal liver. [13]…”