Skip to main content
SpringerLink
Log in

Differentiation of cell types in the mammalian kidney by immunofluorescence microscopy using antibodies to intermediate filament proteins and desmoplakins

  • Published:
Histochemistry Aims and scope Submit manuscript

Summary

The distribution of diverse types of intermediate filaments and desmosomal plaque proteins in rat and bovine kidney has been studied by immunofluorescence microscopy on cryostat sections using antibodies to vimentin, desmin, various preparations of epidermal prekeratins, hepatic cytokeratins as well as a monoclonal cytokeratin antibody which recognizes a wide range of different cytokeratin polypeptides. These immunocytochemical reactions have revealed an unexpected cell type complexity in terms of intermediate filament composition. Vimentin-positive cells are identified as interstitial fibroblasts, capillary endothelia and other vascular wall cells as well as practically all glomerular cells, including podocytes and mesangial cells. Co-existence of vimentin and desmin filaments has been found in glomerular and extra-glomerular mesangial cells, in agreement with the notion that these cells are derived from a specific subset of vascular smooth cells simultaneously expressing vimentin and desmin.

Unexpected differentiations of staining with antibodies to cytokeratins and desmoplakins are noted in the various kidney epithelia. The epithelial cells of Bowman's capsule are heterogeneous in that most cells do not stain with any of the antibodies applied but one group of parietal Bowman's capsule cells forms a conspicuous “crescent” strongly stained with cytokeratin antibodies which so far has not been distinguished from other parietal Bowman's capsule cells by ultrastructural criteria. Certain parts of the nephron such as the proximal convoluted tubule, the descending thin limbs of long loops, the ascending thick limb, and the distal convoluted tubule show poor, if any staining with antibodies to cytokeratins and desmoplakins. By contrast, the straight part of the proximal tubule, the descending thin limbs of short loops, the macula densa, the connecting tubules and the collecting ducts are well stained with antibodies to cytokeratins and desmoplakins, allowing further differentiations according to the specific intracellular distribution of cytokeratin density (apical vs. basolateral vs. general cytoplasmic). The distribution of strong and weak staining tubular segments roughly correlates with the degree of cellular interdigitation of the epithelium. Connecting tubules and collecting ducts show particularly strong staining with cytokeratin antibodies, the highest intensity being characteristic of the collecting duct principal cells. The mesothelial layer covering the organ is also positive for cytokeratins.

The distribution of intermediate filaments and desmosomal plaque proteins in the kidney is discussed in relation to the formation of this organ from embryonal mesenchyme, a cell type that only contains intermediate filaments of the vimentin type. The differences of staining with antibodies to cytokeratins and desmoplakins in the various kidney epithelia are also discussed in relation to morphological differences of epithelial organization and regional differences of function. Our immunocytochemical data suggest that cytokeratins of kidney tubules are different from epidermal prekeratins and are more closely related to those of other simple epithelial cells such as hepatocytes and intestinal mucosa. They also indicate differences of cytokeratin filaments in different parts of the nephron. The value of the use of these antibodies against cytoskeletal proteins in the differentiation of normal and pathologically altered kidney cells, including tumors, is emphasized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altmannsberger M, Osborn M, Hölscher A, Schauer A, Weber K (1981) The distribution of keratin type intermediate filaments in human breast cancer; an immunohistological study. Virchows Arch (Cell Pathol) 37:277–284

    Google Scholar 

  • Andertoon BH (1981) Intermediate filaments: a family of homologous structures. J Muscle Res Cell Motil 2:141–166

    Google Scholar 

  • Asch BB, Burstein NA, Vidrich A, Sun TT (1981) Identification of mouse mammary epithelial cells by immunofluorescence with rabbit and guinea pig antikeratin antisera. Proc Natl Acad Sci USA 7:5643–5647

    Google Scholar 

  • Bachmann S, Kriz W (1982) Histotopography and ultrastructure of the thin limbs of the loop of Henle in the hamster. Cell Tissue Res 225:111–127

    Google Scholar 

  • Bannasch P, Zerban H, Schmid E, Franke WW (1980) Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments. Proc Natl Acad Sci USA 77:4948–4952

    Google Scholar 

  • Bargmann W (1978) Handbuch der mikroskopischen Anatomie des Menschen. Bd 7, 5: Niere und ableitende Harnwege. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Battifora H, Sun TT, Bahu RM, Rao S (1980) The use of antikeratin antiserum as a diagnostic tool: thymoma versus lymphoma. Human Pathol 11:635–641

    Google Scholar 

  • Bennett GS, Fellini SA, Croop JM, Otto JJ, Bryan J, Holtzer H (1978) Differences among the 100 Å filament subunits from different cell types. Proc Natl Acad Sci USA 75:4364–4368

    Google Scholar 

  • Berner PF, Frank E, Holtzer H, Somlyo AP (1981) The intermediate filament proteins of rabbit vascular smooth muscle, immunofluorescent studies of desmin and vimentin. J Muscle Res Cell Motil 2:439–452

    Google Scholar 

  • Berry CA (1982) Heterogeneity of tubular transport processes in the nephron. Annu Rev Physiol 44:181–201

    Google Scholar 

  • Bucher O, Kaissling B (1973) Morphologie des juxtaglomerulären Apparates. Verh Anat Ges 67:109–136

    Google Scholar 

  • Bulger RE, Nagle RB (1973) Ultrastructure of the interstitium in the rabbit kidney. Am J Anat 136:183–204

    Google Scholar 

  • Eckblom P (1981) Determination and differentiation of the nephron. Med Biol 59:139–160

    Google Scholar 

  • Frank ED, Warren L (1981) Aortic smooth muscle cells contain vimentin instead of desmin. Proc Natl Acad Sci USA 78:3020–3024

    Google Scholar 

  • Frank ED, Tuszynski GP, Warren L (1982) Localization of vimentin and desmin in BHK 21/C13 cells and in baby hamster kidney. Exp Cell Res 139:235–247

    Google Scholar 

  • Franke WW, Schmid E, Osborn M, Weber K (1978a) Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Proc Natl Acad Sci USA 75:5034–5038

    Google Scholar 

  • Franke WW, Weber K, Osborn M, Schmid E, Freudenstein C (1978b) Antibody to prekeratin. Decoration of tonofilament-like arrays in various cells of epithelial character. Exp Cell Res 116:429–445

    Google Scholar 

  • Franke WW, Appelhans B, Schmid E, Freudenstein C, Osborn M, Weber K (1979a) Identification and characterization of epithelial cells in mammalian tissues by immunofluorescence microscopy using antibodies to prekeratin. Differentiation 15:7–25

    Google Scholar 

  • Franke WW, Appelhans B, Schmid E, Freudenstein C, Osborn M Weber K (1979b) The organization of cytokeratin filaments in the intestinal epithelium. Eur J Cell Biol 19:255–268

    Google Scholar 

  • Franke WW, Schmid E, Winter S, Osborn M, Weber K (1979c) Widespread occurence of intermediate-sized filaments of the vimentin-type in cultured cells from diverse vertebrates. Exp Cell Res 123:25–46

    Google Scholar 

  • Franke WW, Schmid E, Kartenbeck J, Mayer D, Hacker HJ, Bannasch P, Osborn M, Weber K, Denk H, Wanson JC, Drochmans P (1979d) Characterization of intermediate-sized filaments in liver cells by immunofluorescence microscopy. Biol Cell 34:99–110

    Google Scholar 

  • Franke WW, Schmid E, Freudenstein C, Appelhans B, Osborn M, Weber K, Keenan TW (1980) Intermediate-sized filaments of the prekeratin type in myoepithelial cells. J Cell Biol 84:633–654

    Google Scholar 

  • Franke WW, Denk H, Kalt R, Schmid E (1981a) Biochemical and immunological indentification of cytokeratin proteins in hepatocytes of mammalian liver tissue. Exp Cell Res 131:299–318

    Google Scholar 

  • Franke WW, Schiller DL, Moll R, Winter S, Schmid E, Engelbrecht I, Denk H, Krepler R, Platzer B (1981b) Diversity of cytokeratins: differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol 153:933–959

    Google Scholar 

  • Franke WW, Winter S, Grund C, Schmid E, Schiller DL, Jarasch ED (1981c) Isolation and characterization of desmosome-associated tonofilaments from rat intestinal brush border. J Cell Biol 90:116–127

    Google Scholar 

  • Franke WW, Schmid E, Grund C, Mueller H, Engelbrecht I, Moll R, Stadler J, Jarasch ED (1981d) Antibodies to high molecular weight polypeptides of desmosomes: specific localization of a class of junctional proteins in cells and tissues. Differentiation 20:217–241

    Google Scholar 

  • Franke WW, Grund C, Kuhn C, Jackson BW, Illmensee K (1982a) Formation of cytoskeletal elements during mouse embryogenesis. III. Primary mesenchymal cells and the first appearance of vimentin filaments. Differentiation 23:43–59

    Google Scholar 

  • Franke WW, Moll R, Schiller DL, Schmid E, Kartenbeck J, Mueller H (1982b) Desmoplakins of epithelial and myocardial desmosomes are immunologically and biochemically related. Differentiation 23 (in press)

  • Franke WW, Schmid E, Grund C, Geiger B (1982c) Intermediate filament proteins in nonfilamentous structures: transient disintegration and inclusion of subunit proteins in granular aggregates. Cell 86:103–113

    Google Scholar 

  • Franke WW, Schmid E, Schiller DL, Winter S, Jarasch ED, Moll R, Denk H, Jackson BW, Illmensee K (1982d) Differentiation-related patterns of expression of proteins of intermediate-sized filaments in tissues and cultured cells. Cold Spring Harbor Symp Quant Biol 46:431–453

    Google Scholar 

  • Franke WW, Moll R, Mueller H, Schmid E, Kuhn C, Krepler R, Artlieb U, Denk H (1983) Immunocytochemical identification of epithelium-derived human tumors using antibodies to desmosomal plaque proteins. Proc Natl Acad Sci USA (in press)

  • Fuchs E, Green H (1981) Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell 25:617–625

    Google Scholar 

  • Gabbiani G, Schmid E, Winter S, Chaponier C, De Chastonay C, Vandekerckhove J, Weber K, Franke WW (1981) Vascular smooth muscle cells differ from other smooth muscle cells: Predominance of vimentin filaments and a specific α-type actin. Proc Natl Acad Sci USA 78:298–302

    Google Scholar 

  • Ganote CE, Granham JJ, Moses HL, Burg MB, Orloff J (1968) Ultrastructural studies of vasopressin effect on isolated perfused renal collecting tubules of the rabbit. J Cell Biol 36:355–367

    Google Scholar 

  • Gigi O, Geiger B, Eshhar Z, Moll R, Schmid E, Winter S, Schiller DL, Franke WW (1982) Detection of a cytokeratin determinant common to diverse epithelial cells by a broadly-cross reacting monoclonal antibody. Embo J 1:1429–1437

    Google Scholar 

  • Granger BL, Lazarides E (1979) Desmin and vimentin co-exist at the periphery of the myofibril z-disc. Cell 18:1053–1063

    Google Scholar 

  • Grantham JJ, Burg MB (1966) Effect of vasopressin and cyclic AMP on permeability of isolated collecting tubules. Am J Physiol 211:255–259

    Google Scholar 

  • Holtzer H, Bennett GS, Tapscott SJ, Croop JM, Toyama Y (1982) Intermediate-sized filaments: changes in synthesis and distribution in cells of the myogenic and neurogenic lineages. Cold Spring Harbor Symp Quant Biol 46:317–329

    Google Scholar 

  • Hynes RO, Destree AT (1978) 10 nm filaments in normal and transformed cells. Cell 13:151–163

    Google Scholar 

  • Ishikawa H, Bischoff R, Holtzer H (1968) Mitosis and intermediate-sized filaments in developing skeletal muscle. J Cell Biol 38:538–555

    Google Scholar 

  • Jackson BW, Grund C, Schmid E, Bürki K, Franke WW, Illmensee K (1980) Formation of cytoskeletal elements during mouse embryogenesis. I. Intermediate filaments of the cytokeratin type and desmosomes in preimplantation embryos. Differentiation 17:161–179

    Google Scholar 

  • Jamison RL, Kriz W (1982) Urinary concentrating mechanism. Structure and function. Oxford University Press, New York

    Google Scholar 

  • Kaissling B, Kriz W (1979) Structural analysis of the rabbit kidney. Adv Anat Embryol Cell Biol 56:1–123

    Google Scholar 

  • Kaissling B, Kriz W (1982) Variability of intercellular spaces between macula densa cells; a transmission electron microscopic study in rabbits and rats. Kidney Int 22:9–17

    Google Scholar 

  • Kasimierczak J (1971) Development of the renal corpuscle and the juxtaglomerular apparatus. Acta Pathol Microbiol Scand A, Suppl 218

  • Knepper M, Burg M (1983) Organization of nephron function. Am J Physiol (in press)

  • Kriz W, Kaissling B (1983) Structural organization of the mammalian kidney. In: Giebisch G, Seldin DW (eds) Physiology and pathology of electrolyte metabolism. Raven Press, New York

    Google Scholar 

  • Kriz W, Kaissling B, Psczolla M (1978) Morphological characterization of the cells in Henle's loop and the distal tubule. In: Vogel HG, Ullrich KJ (eds) New aspects of renal function Excerpta Medica, Amsterdam-Oxford (Workshop conferences Hoechst, Vol 6, pp 67–68)

    Google Scholar 

  • Kriz W, Schiller A, Kaissling B (1980) Comparative and functional aspects of thin loop limb ultrastructure. In: Maunsbach AB et al. (eds) Functional ultrastructure of the kidney. Academic Press, London, pp 239–250

    Google Scholar 

  • Lacy ER, Schmidt-Nielsen B (1979) Ultrastructural organization of the hamster renal pelvis. Am J Anat 155:404–424

    Google Scholar 

  • Lazarides E (1980) Intermediate filaments as mechanical integrators of cellular space. Nature 283:249–256

    Google Scholar 

  • Lazarides E (1982) Intermediate filaments: A chemically heterogeneous developmentally regulated class of proteins. Annu Rev Biochem 51:219–250

    Google Scholar 

  • Lazarides E, Hubbard BD (1976) Immunological characterization of the subunit of the 100 Å filaments from muscle cells. Proc Natl Acad Sci USA 76:4344–4348

    Google Scholar 

  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24

    Google Scholar 

  • Osborn M, Geisler N, Shaw G, Sharp G, Weber K (1982) Intermediate filaments. Cold Spring Harbor Symp Quant Biol 46:413–429

    Google Scholar 

  • Paetau A, Virtanen I, Stenman S, Kurki P, Linder E, Vaheri A, Westmark B, Dahl D, Haltia M (1979) Glial fibrillary acidic protein and intermediate filaments in human glioma cells. Acta Neuropathol 47:71–74

    Google Scholar 

  • Paulin D, Babinet C, Weber K, Osborn M (1980) Antibodies as probes of cellular differentiation and cytoskeletal organization in the mouse blastocysl. Exp Cell Res 130:297–304

    Google Scholar 

  • Potter EL (1972) Normal and abnormal development of the kidney. Year Book Medical, Chicago

    Google Scholar 

  • Quinlan RA, Franke WW (1982) Heteropolymer filaments of vimentin and desmin in vascular smooth muscle tissue and cultured baby hamster kidney cells demonstrated by chemical crosslinking. Proc Natl Acad Sci USA 79:3452–3456

    Google Scholar 

  • Ramaekers FCS, Puts JJG, Kant A, Moesker O, Jap PHK, Vooijs GP (1982) Use of antibodies to intermediate filaments in the characterization of human tumors. Cold Spring Harbor Symp Quant Biol 46:331–339

    Google Scholar 

  • Schlegel R, Banks-Schlegel S, McLeod JA, Pinkus GS (1980a) Immunoperoxidase localization of keratin in human neoplasms. Am J Pathol 110:41–49

    Google Scholar 

  • Schlegel R, Banks-Schlegel S, Pinkus GS (1980b) Immunohistochemical localization of keratin in normal human tissues. Lab Invest 42:91–96

    Google Scholar 

  • Schmid E, Tapscott S, Bennett GS, Croop J, Fellini SA, Holtzer H, Franke WW (1979) Differential location of different types of intermediate-sized filaments in various tissues of the chicken embryo. Differentiation 15:27–40

    Google Scholar 

  • Schmid E, Osborn M, Rungger-Brändle E, Gabbiani G, Weber K, Franke WW (1982) Distribution of vimentin and desmin filaments in smooth muscle tissue of mammalian and avian aorta. Exp Cell Res 137:329–340

    Google Scholar 

  • Schmid E, Schiller DL, Grund C, Stadler J, Franke WW (1983) Tissue type specific expression of intermediate filament proteins in a cultured epithelial cell line from bovine mammary gland. J Cell Biol 96:37–50

    Google Scholar 

  • Schnitzer J, Franke WW, Schachner M (1981) Immunocytochemical demonstration of vimentin in astrocytes and ependymal cells of developing and adult mouse nervous system. J Cell Biol 90:435–447

    Google Scholar 

  • Sharp G, Osborn M, Weber K (1982) Occurrence of two different intermediate filament proteins in the same filament in situ within a human glioma cell line. Exp Cell Res 141:385–395

    Google Scholar 

  • Small JV, Sobieszek A (1977) Studies on the function and composition of the 10 nm (100 Å) filaments of vertebrate smooth muscle. J Cell Sci 23:243–268

    Google Scholar 

  • Starger JM, Brown WE, Goldman AE, Goldman RD (1978) Biochemical and immunological analysis of rapidly purified 10 nm filaments from baby hamster kidney (BHK-21) cells. J Cell Biol 78:93–109

    Google Scholar 

  • Sun TT, Green H (1978) Immunofluorescent staining of keratin fibres in cultured cells. Cell 14:469–476

    Google Scholar 

  • Sun TT, Shih CH, Green H (1979) Keratin cytoskeletons in epithelial cells of internal organs. Proc Natl Acad Sci USA 76:2813–2817

    Google Scholar 

  • Tuszynski GP, Franke ED, Damsky CH, Buck CA, Warren L (1979) The detection of smooth muscle desmin-like protein in BHK-21/C-13 fibroblasts. J Biol Chem 254:6138–6143

    Google Scholar 

  • Valtin H (1977) Structural and functional heterogeneity of mammalian nephrons. Am J Physiol 233:F491-F501

    Google Scholar 

  • Vandekerckhove J, Weber C (1979) The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle. Differentiation 14:123–133

    Google Scholar 

  • Winter S, Jarasch ED, Schmid E, Franke WW, Denk H (1980) Differences in polypeptide composition of cytokeratin filaments, including tonofilaments, from different epithelial tissues and cells. Eur J Cell Biol 22:371

    Google Scholar 

  • Wu YJ, Rheinwald JG (1981) A new small (40 kd) keratin filament protein made by some cultured human squamous cell carcinomas. Cell 25:627–635

    Google Scholar 

  • Yen S, Fields KL (1981) Antibodies to neurofilaments, glial filament, and fibroblast intermediate filament proteins bind to different cell types of the neurons system. J Cell Biol 88:115–126

    Google Scholar 

  • Zamboni L, De Martino C (1968) A re-evaluation of the mesangial cells of the renal glomerulus. Z Zellforsch 86:364

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy I, University of Heidelberg, Im Neuenheimer Feld 307, D-6900, Heidelberg, Federal Republic of Germany

    S. Bachmann & W. Kriz

  2. Division of Membrane Biology and Biochemistry, Institute of Cell and Tumor Biology, German Cancer Research Center, Im Neuenheimer Feld 280, D-6900, Heidelberg, Federal Republic of Germany

    C. Kuhn & W. W. Franke

Authors
  1. S. Bachmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Kriz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Kuhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. W. Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bachmann, S., Kriz, W., Kuhn, C. et al. Differentiation of cell types in the mammalian kidney by immunofluorescence microscopy using antibodies to intermediate filament proteins and desmoplakins. Histochemistry 77, 365–394 (1983). https://doi.org/10.1007/BF00490899

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00490899

Keywords

Search

Navigation