Effect of Kupffer cell phagocytosis of erythrocytes and erythrocyte ghosts on susceptibility to endotoxemia and bacteremia

Abstract

The phagocytosis of erythrocytes by macrophages has previously been shown to depress macrophage function. In this study we compared the effect of the phagocytosis of erythrocytes and erythrocyte ghosts by Kupffer cells on the duration of the depression of complement receptor clearance function and host defense against endotoxemia and bacteremia. Phagocytosis of erythrocytes and erythrocyte ghosts was induced in rats by the injection of rat erythrocytes or erythrocyte ghosts coated with anti-rat erythrocyte immunoglobulin G (EIgG and GIgG, respectively). The hepatic uptake of EIgG and GIgG (17.4 X 10(8)/100 g) occurred during the first 30 min after injection. The digestion of phagocytized EIgG and GIgG, as assessed by electron microscopy, was complete at 24 and 3 h after injection, respectively. The depression of Kupffer cell complement receptor clearance function caused by EIgG and GIgG returned to normal by 6 h after injection of EIgG and by 3 h after injection of GIgG. Phagocytosis of EIgG depressed the survival rate after endotoxemia and bacteremia when endotoxin or bacteria were injected at 30 min after EIgG. The survival rate returned to normal when the endotoxin and bacteria were injected at 12 and 6 h after the EIgG, respectively. Phagocytosis of GIgG did not depress the survival rate after endotoxemia and bacteremia. Thus, compared with erythrocytes, erythrocyte ghosts are more rapidly digested after phagocytosis, depress complement receptor function for a shorter period of time, and cause less depression of host defense. These findings indicate that the contents of erythrocytes play an important role in the impairment of host defense caused by the phagocytosis of erythrocytes by Kupffer cells.