A. Brouwer

Clearance Capacity of Rat Liver Kupffer, Endothelial, and Parenchymal Cells

The clearance of five radioactively labeled test substances--polyvinylpyrrolidone, colloidal albumin, antimony sulfur colloid, endotoxin, and heparin--by the reticuloendothelial system was studied after i.v. injection of these substances into rats. The participation of parenchymal, Kupffer, and endothelial liver cells could be determined after isolation and purification of these cell classes. Only endotoxin was almost exclusively taken up by Kupffer cells. All other substances were also taken up by both endothelial and parenchymal cells. From the rate of uptake, expressed as the endocytic index, it appeared that all substances, with the exception of polyvinylpyrrolidone, were taken up by adsorptive endocytosis. Although the specific rate of uptake by parenchymal cells was always slower than that shown by both Kupffer and endothelial cells, the total contribution of parenchymal cells to the clearance of polyvinylpyrrolidone, antimony sulfur colloid, and heparin by the liver was even greater than that of the other two cell classes. The results demonstrate that nonphagocytosing parenchymal and endothelial cells make an important contribution to the clearance of the various test substances which, in addition, is highly dependent on the nature of the substance used. This necessitates a revision of present concepts of clearance by the reticuloendothelial system.

Isolation and culture of Kupffer cells from human liver: Ultrastructure, endocytosis and prostaglandin synthesis

Kupffer cells and other sinusoidal cells were isolated after perfusion and incubation with pronase and collagenase of pieces of liver tissue obtained from organ donors. The resulting cell preparations contained endothelial cells, Kupffer cells and fat-storing cells as well as considerable numbers of leucocytes. Attempts to purify the different sinusoidal cell types by density centrifugation and centrifugal elutriation were successful only for Kupffer cells. Kupffer cells, in contrast to endothelial cells and fat-storing cells, could be kept in maintenance culture for at least 5 days. Cultured Kupffer cells were active in the endocytosis of foreign substances, such as colloidal carbon, latex beads, horseradish peroxidase and bacterial endotoxin. The cultured Kupffer cells synthesized and secreted considerable amounts of prostaglandins PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2. The production of prostaglandins was influenced by the presence of Escherichia coli endotoxin.

Enhancement of Tissue-type Plasmhogen Activator Levels by Retinoids in Rat Tissues in Vivo

We have previously reported that retinoids (vitamin A and derivatives) stimulate the synthesis of tissue-type plasminogen activator (tPA) but not PA inhibitor 1 (PAI-1) in cultured human endothelial cells. * To assess whether a similar effect could be obtained in h, female rats were fed retinoids for various periods of time, and the plasma and tissue concentrations of tPA and PAI-1 were determined.