Skip to main content
The Journal of Biophysical and Biochemical Cytology logoLink to The Journal of Biophysical and Biochemical Cytology
. 1960 Apr 1;7(2):297–304. doi: 10.1083/jcb.7.2.297

Segregation of Ferritin in Glomerular Protein Absorption Droplets

Marilyn G Farquhar 1, George E Palade 1
PMCID: PMC2224798  PMID: 13821609

Abstract

Ferritin was used as a tracer to study the mechanism by which proteins are segregated into droplets by the visceral epithelium of glomerular capillaries. In glomeruli from both normal and aminonucleoside-nephrotic rats ferritin molecules introduced into the general circulation penetrated the endothelial openings and were seen at various levels in the basement membrane. Striking differences between nephrotic and controls were seen only in the amount of ferritin incorporated into the epithelium. In normal animals, a few ferritin molecules were seen in small invaginations of the cell membrane limiting the foot processes, within minute vesicles in the epithelium, or within occasional large vacuoles and dense bodies. In nephrotics, epithelial pinocytosis was marked, and numerous ferritin molecules were seen within membrane invaginations and in small cytoplasmic vesicles at all time points. After longer intervals, the concentration of ferritin increased in vacuoles and particularly within the dense bodies or within structures with a morphology intermediate between that of vacuoles and dense bodies. In nephrotic animals cleft-like cavities or sinuses were frequently encountered along the epithelial cell surface facing the urinary spaces. Some of these sinuses contained material resembling that filling the dense bodies except that it appeared less compact. The findings suggest that ferritin molecules—and presumably other proteins which penetrate the basement membrane—are picked up by the epithelium in pinocytotic vesicles and transported via the small vesicles to larger vacuoles which are subsequently transformed into dense bodies by progressive condensation. The content of the dense bodies may then undergo partial digestion and be extruded into the urinary spaces where it disperses. The activity of the glomerular epithelium in the incorporation and segregation of protein is similar in normal and nephrotic animals, except that the rate is considerably higher in nephrosis where the permeability of the glomerular basement membrane is greatly increased.

Full Text

The Full Text of this article is available as a PDF (2.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CAULFIELD J. B. Effects of varying the vehicle for OsO4 in tissue fixation. J Biophys Biochem Cytol. 1957 Sep 25;3(5):827–830. doi: 10.1083/jcb.3.5.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CHAPMAN-ANDRESEN C. Pinocytosis of inorganic salts by Amoeba proteus (Chaos diffluens). C R Trav Lab Carlsberg Chim. 1958;31(6):77–92. [PubMed] [Google Scholar]
  3. DAVIES J. Cytological evidence of protein absorption in fetal and adult mammalian kidneys. Am J Anat. 1954 Jan;94(1):45–71. doi: 10.1002/aja.1000940103. [DOI] [PubMed] [Google Scholar]
  4. DE DUVE C., PRESSMAN B. C., GIANETTO R., WATTIAUX R., APPELMANS F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955 Aug;60(4):604–617. doi: 10.1042/bj0600604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DE HARVEN E. A new technique for carbon films. J Biophys Biochem Cytol. 1958 Jan 25;4(1):133–134. doi: 10.1083/jcb.4.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FARQUHAR M. G., VERNIER R. L., GOOD R. A. An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus. J Exp Med. 1957 Nov 1;106(5):649–660. doi: 10.1084/jem.106.5.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FARQUHAR M. G., VERNIER R. L., GOOD R. A. Studies on familial nephrosis. II. Glomerular changes observed with the electron microscope. Am J Pathol. 1957 Jul-Aug;33(4):791–817. [PMC free article] [PubMed] [Google Scholar]
  8. FARRANT J. L. An electron microscopic study of ferritin. Biochim Biophys Acta. 1954 Apr;13(4):569–576. doi: 10.1016/0006-3002(54)90376-5. [DOI] [PubMed] [Google Scholar]
  9. FELDMAN J. D., FISHER E. R. Renal lesions of aminonucleoside nephrosis as revealed by electron microscopy. Lab Invest. 1959 Mar-Apr;8(2):371–385. [PubMed] [Google Scholar]
  10. FIEGELSON E. B., DRAKE J. W., RECANT L. Experimental aminonucleoside nephrosis in rats. J Lab Clin Med. 1957 Sep;50(3):437–446. [PubMed] [Google Scholar]
  11. FRENK S., ANTONOWICZ I., CRAIG J. M., METCOFF J. Experimental nephrotic syndrome induced in rats by aminonucleoside; renal lesions and body electrolyte composition. Proc Soc Exp Biol Med. 1955 Jul;89(3):424–427. doi: 10.3181/00379727-89-21833. [DOI] [PubMed] [Google Scholar]
  12. Hunter W. C., Roberts J. M. Glomerular Changes in the Kidneys of Rabbits and Monkeys Induced by Uranium Nitrate, Mercuric Chloride and Potassium Bichromate. Am J Pathol. 1932 Nov;8(6):665–688.5. [PMC free article] [PubMed] [Google Scholar]
  13. NOVIKOFF A. B., BEAUFAY H., DE DUVE C. Electron microscopy of lysosomerich fractions from rat liver. J Biophys Biochem Cytol. 1956 Jul 25;2(4 Suppl):179–184. [PMC free article] [PubMed] [Google Scholar]
  14. OLIVER J., MACDOWELL M. Cellular mechanisms of protein metabolism in the nephron. VII. The characteristics and significance of the protein absorption droplets (hyaline droplets) in epidemic hemorrhagic fever and other renal diseases. J Exp Med. 1958 May 1;107(5):731–754. doi: 10.1084/jem.107.5.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. OLIVER J., MACDOWELL M., LEE Y. C. Cellular mechanisms of protein metabolism in the nephron. I. The structural aspects of proteinuria; tubular absorption, droplet formation, and the disposal of proteins. J Exp Med. 1954 Jun 1;99(6):589–604. doi: 10.1084/jem.99.6.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. PALADE G. E. A study of fixation for electron microscopy. J Exp Med. 1952 Mar;95(3):285–298. doi: 10.1084/jem.95.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. PALADE G. E., SIEKEVITZ P. Liver microsomes; an integrated morphological and biochemical study. J Biophys Biochem Cytol. 1956 Mar 25;2(2):171–200. doi: 10.1083/jcb.2.2.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. PEACHEY L. D. A device for staining tissue sections for electron microscopy. J Biophys Biochem Cytol. 1959 May 25;5(3):511–513. doi: 10.1083/jcb.5.3.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. RICHTER G. W. A study of hemosiderosis with the aid of electron microscopy; with observations on the relationship between hemosiderin and ferritin. J Exp Med. 1957 Aug 1;106(2):203–218. doi: 10.1084/jem.106.2.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. ROSE G. G. Microkinetospheres and VP satellites of pinocytic cells observed in tissue cultures of Gey's strain HeLa with phase contrast cinematographic techniques. J Biophys Biochem Cytol. 1957 Sep 25;3(5):697–704. doi: 10.1083/jcb.3.5.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. ROUILLER C. Les canalicules biliaires; etude au microscope électronique. C R Seances Soc Biol Fil. 1954 Dec;148(23-24):2008–2011. [PubMed] [Google Scholar]
  22. SELLERS A. L., SMITH S., 3rd, MARMORSTON J., GOODMAN H. C. Studies on the mechanism of experimental proteinuria. J Exp Med. 1952 Dec;96(6):643–652. doi: 10.1084/jem.96.6.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. STRAUS W. Changes in droplet fractions from rat kidney cells after intraperitoneal injection of egg white. J Biophys Biochem Cytol. 1957 Nov 25;3(6):933–947. doi: 10.1083/jcb.3.6.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. STRAUS W. Colorimetric analysis with N, N-dimethyl-p-phenylenediamine of the uptake of intravenously injected horseradish peroxidase by various tissues of the rat. J Biophys Biochem Cytol. 1958 Sep 25;4(5):541–550. doi: 10.1083/jcb.4.5.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. STRAUS W. Rapid cytochemical identification of phagosomes in various tissues of the rat and their differentiation from mitochondria by the peroxidase method. J Biophys Biochem Cytol. 1959 Mar 25;5(2):193–204. doi: 10.1083/jcb.5.2.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. STRAUS W. Segregation of an intravenously injected protein by droplets of the cells of rat kidneys. J Biophys Biochem Cytol. 1957 Nov 25;3(6):1037–1040. doi: 10.1083/jcb.3.6.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smetana H. The Permeability of the Renal Glomeruli of Several Mammalian Species to Labelled Proteins. Am J Pathol. 1947 Mar;23(2):255–267. [PMC free article] [PubMed] [Google Scholar]
  28. VERNIER R. L., PAPERMASTER B. W., GOOD R. A. Aminonucleoside nephrosis. I. Electron microscopic study of the renal lesion in rats. J Exp Med. 1959 Jan 1;109(1):115–126. doi: 10.1084/jem.109.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. WATSON M. L. Reduction of heating artifacts in thin sections examined in the electron microscope. J Biophys Biochem Cytol. 1957 Nov 25;3(6):1017–1022. doi: 10.1083/jcb.3.6.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. WATSON M. L. Staining of tissue sections for electron microscopy with heavy metals. II. Application of solutions containing lead and barium. J Biophys Biochem Cytol. 1958 Nov 25;4(6):727–730. doi: 10.1083/jcb.4.6.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. WILSON S. G., HACKEL D. B., HORWOOD S., NASH G., HEYMANN W. Aminonucleoside nephrosis in rats. Pediatrics. 1958 Jun;21(6):963–973. [PubMed] [Google Scholar]

Articles from The Journal of Biophysical and Biochemical Cytology are provided here courtesy of The Rockefeller University Press

RESOURCES