On the cell biology of pit cells, the liver-specific NK cells.

Abstract

There is s growing evidence that pit cells are highly active, liver-specific NK cells. Pit cells are located in the liver sinusoids and can be easily isolated and purified by liver sinusoidal lavage and a magnetic separation method. Furthermore, pit cells can be separated into a LD and HD fraction by 45% iso-osmotic Per coll gradient centrifugation. These two populations are shown to differ morphol ogically, phenotypically and functionally from each other and from blood NK cells. LD pit cells contain more rod-cored vesicles and more, but smaller granules than blood NK cells although both of them share LGL morphology. Phenotypically, LD cells have a higher expression of LFA-1 and a lower expression of asialo-GM 1 molecules compared to blood or spleen NK cells. Functionally, pit cells are more cytotoxic against several tumor cell lines as compared to blood NK cells, and are able to kill-NK-resistant but LAK-sensitive P815 cells. These data indicate that pit cells are a kind of naturally activated NK cells and their cytotoxic function is comparable to IL-2 in vitro activated NK cells. The characteristics of HD cells are intermediate between LD pit cells and blood NK cells. Pit cells most probably originate from blood NK cells, although they show mitosis in the liver after certain stimuli. The recruitment of pit cells in the liver is mediated by adhesion molecules. A major challenge is to achieve a better understanding of the mechanisms of pit cell cytotoxicity and the cooperation between pit cells and other cells in the liver, i.e. Kc, Ec and LAL. Moreover, since pit cells are located in a strategic position in the hepatic sinusoids, they represent a first line of cellular defense against metastasing colon cancer cells. The role of pit cells in a number of liver pathologies deserves more attention.