Fine structural and cytochemical aspects of granuloma formation derived from Kupffer cells in mice injected with latex particles.

The fate of Kupffer cells in mice for 3 days following injection with polystyrene latex particles (0.2 and 2.0 micron in diameter) was studied by electron microscopy. Kupffer cells took up the latex particles by pinocytosis as well as by phagocytosis. The particles ingested were in contact or fused with lysosomes in the cell. Two days after the final injection, most Kupffer cells were already stuffed with the particles. Within one month, cell clumps or cell aggregates, which could be called granuloma, were formed in the liver connective tissue space, i.e., Disse spaces, interlobular connective tissue spaces and subperitoneal connective tissue spaces. They were mostly composed of cells laden with numerous latex particles. The large granulomas were 80-120 micron in diameter. In each granuloma, endogenous peroxidase was localized in the cisternae of the nuclear envelope and of the rough endoplasmic reticulum of most cells, and in the cytoplasmic granules of some other cells. The former is known to be a Kupffer cell, and the latter, a monocyte. The granuloma further contained a few intermediate cells, showing peroxidase activity in the cisternae of the nuclear envelope and of the rough endoplasmic reticulum, and also in the cytoplasmic granules, phagocytic cells without peroxidase activity, granulocytes, and plasma cells. Hepatic sinusoidal endothelial cells, attenuated in shape, also took up latex particles of a 0.2 micron diameter and rarely with a 2.0 micron diameter in their cytoplasm. Some Kupffer cells in the granuloma filled with numerous latex particles were labeled with 3H-thymidine (2.5 mCi in total dose) after subcutaneous injection ten times for 80 hr. In the animals 8 months after the injection of the latex particles, numerous large granulomas were distributed throughout the liver in the interlobular or subperitoneal connective tissue space. The formation of the granuloma of Kupffer cells is considered to play a great role in the disposing of foreign materials from the functional liver parenchymatous tissue.