Phagocytosis and LPS-stimulated production of cytokines and prostaglandin E2 is different in Kupffer cells isolated from the periportal or perivenous liver region

Background: Kupffer cells can release pro-inflammatory mediators and contribute to damage, which often appears in a zonated fashion. Methods: To assess position-associated functional differences, functions of intact Kupffer cells isolated from either the periportal or perivenous acinar region of rat liver were compared. Results: Kupffer cells from the periportal region phagocytosed 2 - 3 times more FITC-labelled zymosan particles than corresponding perivenous cells, as determined by confocal microscopy and fluorescence assay. Periportal cells also produced more TNF-alpha and IL-1beta, but less NO and PGE(2), compared to perivenous cells and the stimulation by addition of lipopolysaccharides (LPS) was moderate. In contrast, after overnight culture LPS dramatically increased TNF-alpha release and significantly more so in perivenous Kupffer cells (26-fold) than in periportal cells (11-fold). Conclusion: Our study suggests that periportal Kupffer cells are responsible for a major part of phagocytosis by the liver. The stronger LPS response of recovered perivenous Kupffer cells suggests a dominant role of these cells in proinflammatory events that ultimately may contribute to development of damage in this region.