Proteolysis of formaldehyde-treated albumin in Kupffer cells and its inhibition by suramin.

The uptake and breakdown of formaldehyde-treated "'Ior '='I-labeled albumin in liver lysosomes have been measured in vivo. Ultracentrifuge studies and gel filtration showed that, in contrast to heat-denatured albumin frequently used in clearance experiments, our formaldehyde-treated protein did not form aggregates. Nevertheless, it was exclusively taken up in the Kupffer cells as demonstrated b autoradiography. The in vitro breakdown of the protein in the Kupffer cells was inhibited by suramin. The results of determinations of the drug in liver fractions were in agreement with a lysosomal localization. Histochemical staining showed a granular accumulation of suramin in Kupffer cells only. Our results indicate that (1) the hypothesis that denatured serum proteins are rapidly taken up by the reticuloendothelial system because they form aggregates is not tenable; (2) the many reports in literature on intralysosomal breakdown of formaldehyde-treated albumin in vitro and its inhibition by suramin apply exclusively to Kupffer cell lysosomes.