Skip to main content
Log in

Morphology of interstitial cells in the healthy kidney

  • Review Article
  • Published:
Anatomy and Embryology Aims and scope Submit manuscript

Abstract

Renal interstitial cells play an important role in renal function and renal diseases. We describe the morphology of renal interstitial cells in the healthy kidney. We distinguish within the renal interstitium (1) renal fibroblasts and (2) cells of the immune system. Fibroblasts are in the majority and constitute the scaffold of the kidney; they are interconnected by junctions, and are attached to tubules and vessels. Although the phenotype of fibroblasts shows some variation depending on their location in the kidney and on their functional stage, their recognition as fibroblasts is possible on account of structural features. Among the cell types of the second group, antigen-presenting dendritic cells are the most abundant in in the peritubular interstitial spaces of healthy kidneys. Their incidence is highest in the inner stripe of the outer medulla. They share some morphological features with fibroblasts but lack others — junctional complexes, morphologically defined connections with tubules and vessels, and the prominent layer of actin filaments under the plasma membrane — that are characteristic for fibroblasts. Dendritic cells in healthy kidneys are morphologically different from macrophages, which are characterized by abundant primary and secondary lysosomes. In healthy kidneys macrophages are restricted to the connective tissue of the renal capsule and the pelvic wall, and to the periarterial connective tissue. Lymphocytes are rare in healthy kidneys. The distinction of cell types by morphology is supported by differences of membrane proteins. Among all interstitial cells in the renal cortex, fibroblasts alone exhibit ecto-5′-nucleotidase. Dendritic cells constitutively have a high abundance of MHC class II protein. Both proteins are mutually exclusive. Rat macrophages display the membrane antigen ED 2 and lymphocytes exhibit specific surface antigens, depending on their type and functional stage, e.g., CD4 or CD8.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alpers CE, Hudkins KL, Floege J, Johnson RJ (1994) Human renal cortical interstitial cells with some features of smooth muscle cells participate in tubulointerstitial and crescentic glomerular injury. J Am Soc Nephrol 5: 201–210

    Google Scholar 

  • Austyn JM, Hankins DF, Larsen CP, Morris PJ, Rao AS, Roake JA (1994) Isolation and characterization of dendritic cells from mouse heart and kidney. J Immunol 152: 2401–2410

    Google Scholar 

  • Bachmann S, Le Hir M, Eckardt KU (1993) Colocalization of erythropoietin mRNA and ecto-5′-nucleotidase immunoreactivity in peritubular cells of the rat renal cortex suggests that fibroblasts produce erythropoietin. J Histochem Cytochem 41: 335–341

    Google Scholar 

  • Bayreuther K, Francz PI, Gogol J, Hapke C, Maier M, Meinrath H-J (1991) Differentiation of primary and secondary fibroblasts in cell culture systems. Mutat Res 256: 233–242

    Google Scholar 

  • Bellows CG, Melcher AH, Bhargava U, Aubin JE (1982) Fibroblasts contracting three-dimensional collagen gels exhibit ultrastructure consistent with either contraction or protein secretion. J Ultrastruct Res 78: 178–192

    Google Scholar 

  • Bohle A, Christensen J, Kokot F, Osswald H, Schubert B, Kendziorra H, Pressler H, Marcovic-Lipkovski J (1990) Acute renal failure in man: new aspects concerning pathogenesis. a morphometric study. Am J Nephrol 10: 374–388

    Google Scholar 

  • Bohman S-O (1974) The ultrastructure of the rat renal medulla as observed after improved fixation methods. J Ultrastruct Res 47:329–360

    Google Scholar 

  • Bohman S-O (1980) The ultrastructure of the renal medulla and the interstitial cells. In: Mandai AK, Bohman S-O (eds) The renal papilla and hypertension. Plenum Press, New York, pp 7–33

    Google Scholar 

  • Bombara MP, Webb DL, Conrad P, Marlor CW, Sarr T, Ranges GE, Aune TM, Greve JM, Blue M-L (1993) Cell contact between T cells and synovial fibroblasts causes induction of adhesion molecules and cytokines. J Leukoc Biol 54: 399–406

    Google Scholar 

  • Brouwer A, Wisse E, Knook DL (1988) Sinusoidal endothelial cells and perisinusoidal fat-storing cells. In: Arias IM, Jakoby WB, Popper H, Schachter D, Shafritz DA (eds) The liver: biology and pathobiology. Raven Press, New York, pp 665–682

    Google Scholar 

  • Bruijn JA, Heer E de (1995) Adhesion molecules in renal diseases. Lab Invest 72: 387–394

    Google Scholar 

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

    Google Scholar 

  • Bulger RE, Trump BF (1966) Fine structure of the rat renal papilla. Am J Anat 118: 685–722

    Google Scholar 

  • Bulger RE, Griffith LD, Trump BF (1966) Endoplasmic reticulum in rat renal interstitial cells: molecular rearrangement after water deprivation. Science 151: 83–86

    Google Scholar 

  • Burridge K, Fath K, Kelly T, Nuckolls G, Turner C (1988) Focal adhesion: transmembrane junctions between the extracellular matrix and cytoskeleton. Annu Rev Cell Biol 4: 487–525

    Google Scholar 

  • Cameron JSt (1992) Tubular and interstitial factors in the progression of glomerulonephritis. Pediatr Nephrol 6: 292–303

    Google Scholar 

  • Dawson TP, Gandhi R, Le Hir M, Kaissling B (1989) Ecto-5'-nucleotidase: localization by light microscopic histochemistry and immunohistochemistry methods in the rat kidney. J Histochem Cytochem 37: 39–47

    Google Scholar 

  • Desmoulière A, Gabbiani G (1995) Myofibroblast differentiation during fibrosis. Exp Nephrol 3: 134–139

    Google Scholar 

  • Diamond JR, Goor H van, Ding G, Engelmyer E (1995) Myofibroblasts in experimental hydronephrosis. Am J Pathol 146: 121–129

    Google Scholar 

  • Dijkstra CD, Döpp EA, Joling P, Kraal G (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by mononuclear antibodies ED1, ED2 and ED3. Immunology 54: 589–599

    Google Scholar 

  • Eddy AA, McCulloch L, Adams J, Liu E (1989) Interstitial nephritis induced by protein-overload proteinuria. Am J Pathol 135: 719–718

    Google Scholar 

  • Fine LG, Norman JT, Ong A (1995) Cell-cell cross-talk in the pathogenesis of renal interstitial fibrosis. Kidney Int 47 [Suppl 49]: S48-S50

    Google Scholar 

  • Fourman J (1970) The adrenergic innervation of the efferent arterioles and the vasa recta in the mammalian kidney. Experientia 26: 293–294

    Google Scholar 

  • Gandhi R, Le Hir M, Kaissling B (1990) Immunolocalization of ecto-5′-nucleotidase in the kidney by a monoclonal antibody. Histochemistry 95: 165–174

    Google Scholar 

  • Gorgas K (1978) Structure and innervation of the juxtaglomerular apparatus of the rat. Adv Anat Embryol Cell Biol 54: 5–84

    Google Scholar 

  • Hart DNJ, Fabre JW (1981) Major histocompatibility complex antigens in rat kidney, ureter, and bladder. Transplantation 31: 318–325

    Google Scholar 

  • Hashizume T, Imayama S, Hori Y (1993) Scanning electron microscopic study on dendritic cells and fibroblasts in connective tissue. J Electron Microsc (Tokyo) 41: 434–437

    Google Scholar 

  • Hughes AK, Barry WH, Kohan DE (1995) Identification of a contractile function for renal medullary interstitial cells. J Clin Invest 96: 411–416

    Google Scholar 

  • Hughes DA, Fraser IP, Gordon SG (1995) Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs. Eur J Immunol 25: 466–473

    Google Scholar 

  • Kaissling B, Le Hir M (1994) Characterization and distribution of interstitial cell types in the renal cortex of rat. Kidney Int 45: 709–720

    Google Scholar 

  • Kaissling B, Spiess S, Rinne B, Le Hir M (1993) Effects of anemia on the morphology of the renal cortex of rats. Am J Physiol 264: F608-F617

    Google Scholar 

  • Knepper MA, Danielson RA, Saidel GM, Post RS (1977) Quantitative analysis of renal medullary anatomy in rats and rabbits. Kidney Int 12: 205–213

    Google Scholar 

  • Knight SC, Stagg AJ (1993) Antigen-presenting cell types. Curr Opin Immunol 5: 374–382

    Google Scholar 

  • Komuro T (1990) Re-evaluation of fibroblasts and fibroblast-like cells. Anat Embryol 182: 103–112

    Google Scholar 

  • Kriz W, Kaissling B (1992) Structural organization of the mammalian kidney. In: Seidin DW, Giebisch G (eds) The kidney, physiology and pathophysiology. Raven Press, New York, pp 707–777

    Google Scholar 

  • Kriz W, Dieterich HJ (1970) Das Lymphgefässystem der Niere bei einigen Säugetieren: Lichtund elektronmikroskopische Untersuchungen. Z Anat Entwicklungsgesch 131: 111–147

    Google Scholar 

  • Kriz W (1987) A periarterial pathway for intrarenal distribution of renin. Kidney Int Suppl 20: 51–56

    Google Scholar 

  • Kriz W, Napiwotzky P (1979) Structural and functional aspects of the renal interstitium. Contrib Nephrol 16: 104–108

    Google Scholar 

  • Kuncio GS, Neilson EG, Haverty T (1991) Mechanisms of tubulointerstitial fibrosis. Kidney Int 39: 550–556

    Google Scholar 

  • Kurtz A, Eckardt K-U, Neumann R, Kaissling B, Le Hir M, Bauer C (1989) Site of erymropoietin formation. Contrib Nephrol 76: 14–23

    Google Scholar 

  • Le Hir M, Kaissling B (1989) Distribution of 5′nucleotidase in the renal interstitium of the rat. Cell Tissue Res 258: 177–182

    Google Scholar 

  • Le Hir M, Kaissling B (1993) Distribution and regulation of ecto- 5'-nucleotidase in the kidney. Implications for the physiological function of adenosine. Am J Physiol 264: F377-F387

    Google Scholar 

  • Le Hir M, Eckardt K-U, Kaissling B (1989) Anemia induces 5′- nucleotidase in fibroblasts of cortical labyrinth of rat kidney. Renal Physiol Biochem 12: 313–319

    Google Scholar 

  • Le Hir M, Eckardt K-U, Kaissling B, Koury ST, Kurtz A (1991) Structure-function correlations in erymropoietin formation and oxygen sensing in the kidney. Klin Wochenschr 69: 567–575

    Google Scholar 

  • Leczynsky D, Renkonen R, Häyry P (1985) Localization and turnover rate of renal dendritic cells. Am J Anat 21: 355–360

    Google Scholar 

  • Lemley KV, Kriz W (1991) Anatomy of the renal interstitium. Kidney Int 39: 370–382

    Google Scholar 

  • Lonnemann GL, Shapiro G, Engler-Blum G, Muller GA, Koch KM, Dinarello CA (1995) Cytokines in human renal interstitial fibrosis. I, II. Kidney Int. 47: 837–854

    Google Scholar 

  • Lüllmann-Rauch R (1987) Lysosomal storage of sulfated glycosaminoglycans in renal interstitial cells of rats treated with tirolone. Cell Tissue Res 250: 641–648

    Google Scholar 

  • Maxwell PH, Osmond MK, Pugh ChW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DKP, Johnson MH, Ratcliffe PJ (1993) Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int 44: 1149–1162

    Google Scholar 

  • Muirhead EE (1990) Discovery of the renomedullary system of blood pressure control and its hormones. Hypertension 15: 114–116

    Google Scholar 

  • Muirhead EE (1991) The medullipin system of blood pressure control. Am J Hypertens 4: 556S-568S

    Google Scholar 

  • Nagano M, Ishimura K, Fujita H (1988) Fine structural study on the development of the renal medullary interstitial cells (known to secrete antihypertensive factors) of Wistar Kyoto as well as spontaneously hypertensive rats. J Clin Electron Microscopy 21: 223–233

    Google Scholar 

  • Pedersen JC, Persson AEG, Maunsbach AG (1980) Ultrastructure and quantitative characterization of the cortical interstitium in the rat kidney. In: Maunsbach AG, Olsen TS, Christensen EJ (eds) Functional ultrastructure of the kidney. Academic Press, London, pp 443–447

    Google Scholar 

  • Pfaller W (1982) Structure function correlation in rat kidney. Quantitative correlation of structure and function in the normal and injured rat kidney. Adv Anat Embryol Cell Biol 70: 1–106

    Google Scholar 

  • Pinto da Silva P, Gilula NB (1972) Gap junctions in normal and transformed fibroblasts in culture. Exp Cell Res 71: 393–401

    Google Scholar 

  • Postlethwaite AE, Kang AH (1992) Fibroblasts and Matrix Proteins. In: Gallin JI, Goldstein IM, Snyderman R (eds) Inflammation: basic principles and clinical correlates, 2nd edn. Raven Press, New York, pp 747–773

    Google Scholar 

  • Rodemann HP, Müller GA (1991) Characterization of human renal fibroblasts in health and disease. 2. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. Am J Kidney Dis 17: 684

    Google Scholar 

  • Rodemann HP, Müller GA, Knecht A, Norman JT, Fine LG (1991) Fibroblasts of rabbit kidney in culture. I. Characterization and identification of cell-specific marker. Am J Physiol 261: F283-F291

    Google Scholar 

  • Romen W, Thoenes W (1970) Histiocytäre und fibrocytäre Eigenschaften der interstitiellen Zellen der Nierenrinde. Virchows Archiv B Cell Pathol 5: 365–375

    Google Scholar 

  • Sappino AP, Schürch W, Gabbiani G (1990) Different repertoire of fibroblastic cells: expression of cytoskeletal proteins as markers of phenotypic modulations. Lab Invest 63: 144–161

    Google Scholar 

  • Schiller A, Taugner R (1979) Junctions between interstitial cells of the renal medulla: a freeze fracture study. Cell Tissue Res 203: 231–240

    Google Scholar 

  • Skalli O, Schürch W, Seemayer T, Lagace R, Montandon D, Pittet B, Gabbiani G (1989) Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest 60: 275–285

    Google Scholar 

  • Spielman WS, Arend LJ (1991) Adenosine receptors and signalling in the kidney. Hypertension 17: 117–130

    Google Scholar 

  • Squier CA, Bausch WH (1984) Three-dimensional organization of fibroblasts and collagen fibrils in rat tail tendon. Cell Tissue Res 238: 319–327

    Google Scholar 

  • Steiman RM, Swanson J (1995) The endocytic activity of dendritic cells. J Exp Med 182: 283–288

    Google Scholar 

  • Stein-Oakley AN, Jablonski P, Kraft N, Biguzas M, Howard BO, Marshall VC, Thomson NM (1991) Differential irradiation effects on rat interstitial dendritic cells. Transplant Proc 23: 632–634

    Google Scholar 

  • Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9: 271–296

    Google Scholar 

  • Strutz F, Okada H, Lo CW, Danoff T, Carone L, Tomaszewski JE, Neilson EG (1995) Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 130: 393–405

    Google Scholar 

  • Sundelin B, Bohman S-O (1989) Uptake of exogenous protein tracer in cells of the rat renal papilla. Histochemistry 93: 63–68

    Google Scholar 

  • Sundelin B, Bohman SO (1990) Postnatal development of the interstitial tissue of the rat kidney. Anat Embryol 182: 307–317

    Google Scholar 

  • Swann AG, Norman RJ (1970) The periarterial spaces of the kidney. Tex Rep Biol Med 28: 317–334

    Google Scholar 

  • Takahashi-Iwanaga H (1991) The three-dimensional cytoarchitecture of the interstitial tissue in the rat kidney. Cell Tissue Res 264: 269–281

    Google Scholar 

  • Thompson LF, Ruedi JM, O'Connor RD, Bastian JF (1986) Ecto- 5′-nucleotidase expression during human B cell development. An explanation for the heterogeneity in B lymphocyte ecto-5′- nucleotidase activity in patients with hypogammaglobulinemia. J Immunol 137: 2496–2500

    Google Scholar 

  • Tisher CC, Madsen KM (1988) Anatomy of the Renal Interstitium. In: Davison AM, Briggs JD, Green R, Kanis JA, Mallick NP, Rees AJ, Thomson D (eds) Nephrology, vol 1. Proceedings of the Xth International Congress of Nephrology. Baillière Tindall, London, pp 587–598

    Google Scholar 

  • Vernace MA, Mento PF, Maita ME, Girardi EP, Chang MY, Nord EP, Wilkes BM (1995) Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells. J Clin Invest 96: 183–191

    Google Scholar 

  • Vyalov S, Desmoulière A, Gabbiani G (1993) GM-CSF-induced granulation tissue formation: relationships between macrophage and myofibroblast accumulation. Virchows Archiv 63: 231–239

    Google Scholar 

  • Wolf G, Neilson EG (1991) Molecular mechanisms of tubulointerstitial hypertrophy and hyperplasia. Kidney Int 30: 401–420

    Google Scholar 

  • Wolgast M, Larson M, Nygren K (1981) Functional characteristics of the renal interstitium. Am J Physiol 241: F105-F111

    Google Scholar 

  • Yamate J, Tatsumi M, Nakatsuji S, Kuwamura M, Kotani T, Sakuma S (1995) Immunohistochemical observations on the kinetics of macrophages and myofibroblasts in rat renal interstitial fibrosis induced by cis-diaminedichloroplatinum. J Comp Pathol 112: 27–39

    Google Scholar 

  • Zusman RM, Keiser HR (1977) Prostaglandin biosynthesis by rabbit renomedullary interstitial cells in tissue culture. J Clin Invest 60: 215–223

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaissling, B., Hegyi, I., Loffing, J. et al. Morphology of interstitial cells in the healthy kidney. Anat Embryol 193, 303–318 (1996). https://doi.org/10.1007/BF00186688

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00186688

Key words

Navigation