Binding and receptor-mediated endocytosis of pregnancy zone protein-proteinase complex in rat macrophages.
125I-labelled pregnancy zone protein complex was injected intravenously in rats and after 6 min uptake into cells of the liver and spleen was determined by electron microscopic autoradiography. The liver took up 68% of the injected radioactivity; 61% was in the hepatocytes and 7% was in the liver macrophages (Kupffer cells). The spleen took up 3-4% and nearly all the radioactivity was in the macrophages of the red pulp. The uptake per cell volume was several times higher in the macrophage than in the hepatocyte. The radioactivity associated with macrophages was largely in endocytotic vacuoles and lysosomes. Binding of labelled pregnancy zone protein complex to peritoneal macrophages at 4 degrees C was 2-3 times higher than binding of the homologous alpha 2-macroglobulin complex. The two ligands competed for binding to the same receptors and the difference was due to a higher affinity of the pregnancy zone protein complex (Kd approx. 60 pM). After binding to the receptor, this ligand was internalised within 2-3 min at 37 degrees C and radioactivity inside the cells largely represented intact pregnancy zone protein complex. Radioactivity was released from the cell as iodotyrosine after a lag time of about 10 min. It is concluded that pregnancy zone protein complex is bound with a high affinity to the alpha 2-macroglobulin receptors in rat macrophages followed by receptor-mediated endocytosis and degradation of the ligand in the lysosomes.
D000818:Animals; D001345:Autoradiography; D002918:Chymotrypsin / Q000378:metabolism*; D004705:Endocytosis; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D011257:Pregnancy Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism / Q000648:ultrastructure; D000511:alpha-Macroglobulins / Q000378:metabolism
D007457:Iodine Radioisotopes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011257:Pregnancy Proteins; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D002918:Chymotrypsin