低蛋白食飼育マウスにおけるＫｕｐｆｆｅｒ細胞の分化，増殖機序に関する検討

Abstract

Protein calorie malnutrition is known to induce various macrophage dysfunctions. However, little is known about the behavior of Kupffer cells under protein calorie malnutrition in vivo. To investigate them, we fed mice on a low protein diet for four weeks and examined the number, cytological changes, and proliferative capacity of their Kupffer cells. The recovery processes of Kupffer cells in the protein-deprived mice after normal protein feeding were also investigated.In the protein-deprived mice, Kupffer cells decreased in number to two thirds that of the normally fed mice, showed the cytological and ultrastructural features of maturation failure, and had reduced proliferative capacity. Ultrastructural peroxidase (PO) cytochemistry revealed that the intensity of PO activity was weak in the rough endoplasmic reticulum and nuclear envelope of the immature Kupffer cells. The expression of M-CSF mRNA determined by Northern blot analysis in the liver was reduced, while that of GM-CSF m-RNA was not reduced. The serum levels of IL-6 and GM-CSF were increased. After normal protein feeding, the number, morphology, and proliferative capacity of the Kupffer cells in the liver reversed to the normal state, showing matured features as in the normally ted mice. The expression of M-CSF mRNA recovered to the normal level. Colony-forming assays demonstrated that the GM-CFCs and M-CFCs were increased in the bone marrow of the protein-deprived mice but peripheral monocyte was not increased. These results suggest that the reduced production of M-CSF in the liver of protein-deprived mice results in numerical reduction, maturation failure, and decreased proliferative capacity of Kupffer cells.