Kupffer Cell Function in Host Defense

High-resolution in vivo microscopic methods have been used to explore the responses to endotoxin of Kupffer cells in the livers of anesthetized mice, rats, hamsters, and guinea pigs under a variety of experimental conditions. These include studies of normal animals as well as of animals sensitized or tolerant to endotoxin, C3H/HeJ mice with a low re-sponse to endotoxin, mice rendered septic by cecal ligation and puncture, mice with Kupf-fer cells selectively destroyed by frog virus 3, and rats with portacaval shunts. The func-tional state of Kupffer cells was evaluated by measuring both the number of these cells per microscopic field that phagocytosed l.O-llm latex particles and the rate at which in-dividual Kupffer cells phagocytosed single latex particles. The intrahepatic density and level of activation of Kupffer cells were found to playa role in determining endotoxin sensitivity and to be involved, in conjunction with endotoxin, in the development of toler-ance. All of these studies support the concept of a central role for Kupffer cells in host defense mechanisms and of the possible modulation and of this role bygut-derived endo-toxins contained in the portal blood. Kupffer cells are phagocytic cells that constitute on