Lysosomal degradation of cell organelles: IV. Heterophagocytosis and acute inflammation in liver after intravenous injection of isolated liver-cell plasma membranes

Abstract

Isolated liver-cell plasma membranes were injected intravenously into a series of highly inbred rats. The uptake and digestion by Kupffer cells were followed by ultrastructural analysis in order to evaluate the capacity of lysosomes to degrade cellular membranes. By 1 to 5 min following administration, clusters of plasma membranes appeared in the sinusoidal lumens. Invaginations of the Kupffer-cell surfaces in combination with flap-like processes embraced the aggregates and formed endocytic vacuoles. Fibrinous deposits and platelet accumulation were sometimes observed at the surface of the Kupffer cells. At later time points (10 min to 2 hr) an increased number of plasma-membrane derivatives with trilaminar structures still recognizable was observed in large digestive vacuoles. In some focal areas, an acute inflammatory response was noted in the sinusoids often surrounding clusters of fibrin deposits, trapped erythrocytes, and aggregates of plasma membranes and platelets. At 8 hr there was a clearance from some digestive vacuoles of identifiable membranes with the appearance of dense homogeneous material; plasma membranes were still present in the sinusoids together with degranulating and degenerating leukocytes also phagocytizing plasma membranes. By 24 hr most of the inflammatory response had subsided. Many Kupffer cells resembled those in control animals although the digestive vacuoles or residual bodies contained numerous lipid-like droplets presumed to be remnants of membrane lipid digestion. By 2–5 days the Kupffer cells gradually became indistinguishable from the controls and the micropinocytosis vermiformis reappeared. It is concluded that plasma membranes after being phagocytized are digested within lysosomes. In contrast to mitochondria and microsomes ( Glaumann et al., 1975a b; Glaumann and Trump, 1975), intravenous injections of plasma membranes gave rise to focally occurring thrombi which were surrounded by an acute transient inflammatory response.