Summary
This investigation provides histochemical evidence for lysosomal storage of sulfated glycosaminoglycans (GAGs) in the interstitial cells of the renal cortex and in macrophage-like cells of the renal medullary zones of rats chronically treated with the drug tilorone. This compound is known to interfere with lysosomal degradation of sulfated GAGs; therefore cells that develop GAG-storage can be assumed to be involved in the turnover of GAGs. In view of this consideration, the most remarkable and still unexplained finding was that the intrinsic interstitial cells in the papilla, which is known to be particularly rich in sulfated GAGs, did not show the cytological symptoms of lysosomal GAG-storage. The present findings may stimulate further studies focused on the cellular sites of turnover of the sulfated GAGs present in the renal medullary interstitium.
Similar content being viewed by others
References
Bach PH, Bridges JW (1986) Chemically induced renal papillary necrosis and upper urothelial carcinoma. Part 1. CRC Crit Rev Toxicol 15:217–329
Barry DN, Bowness JM (1975) Identification and turnover of glycosaminoglycans in rat kidneys. Can J Biochem 53:713–720
Bohman SO (1974) The ultrastructure of the rat renal medulla as observed after improved fixation methods. J Ultrastruct Res 47:329–360
Buchheim W, Drenckhahn D, Lüllmann-Rauch R (1979) Freezefracture studies of cytoplasmic inlcusions occurring in experimental lipidosis as induced by amphiphilic cationic drugs. Biochim Biophys Acta 575:71–80
Bulger RE, Nagle RB (1973) Ultrastructure of the interstitium in the rabbit kidney. Am J Anat 136:183–203
Dieterich HJ (1968) Die Ultrastruktur der Gefäßbündel im Mark der Rattenniere. Z Zellforsch 84:350–371
Doty SB, Smith CE, Hand AR, Oliver C (1977) Inorganic trimetaphosphatase as a histochemical marker for lysosomes in light and electron microscopy. J Histochem Cytochem 25:1381–1384
Fratantoni JC, Hall CW, Neufeld EF (1968) The defect in Hurler's and Hunter's syndromes: faulty degradation of mucopolysaccharide. Proc Natl Acad Sci USA 60:699–706
Gupta DK, Gieselmann V, Hasilik A, Figura Kv (1984) Tilorone acts as a lysosomotropic agent in fibroblasts. Hoppe-Seyler's Z Physiol Chem 365:859–866
Hein L, Lüllmann-Rauch R, Prokopek M (1987) Mucopolysaccharidosis induced by dicationic amphiphilic drugs. NaunynSchmiedebergs Arch Pharmacol 335:R3
Horstmann G, Lüllmann-Rauch R (1985) Mucopolysaccharidosislike alterations in cardiac valves of rats treated with tilorone. Virchows Arch (Cell Pathol) 48:33–45
Kresse H, Grossmann A (1970) Vergleichende Untersuchung des Mucopolysaccharid- und Kollagengehaltes in verschiedenen topographischen Zonen der Niere von Ratte, Hund und Schwein. Z Klin Chem Klin Biochem 8:420–424
Kresse H, Cantz M, Figura K von, Glössl J, Paschke E (1981) The mucopolysaccharidoses: biochemistry and clinical symptoms. Klin Wochenschr 59:867–876
Lev R, Spicer SS (1964) Specific staining of sulphate groups with alcian blue at low pH. J Histochem Cytochem 12:309
Levine S, Sowinski R (1977) T-lymphocyte depletion and lesions of choroid plexus and kidney induced by tertiary amines in rats. Toxicol Appl Pharmacol 40:147–159
Lüllmann H, Lüllmann-Rauch R, Wassermann O (1978) Lipidosis induced by amphiphilic cationic drugs. Biochem Pharmacol 27:1103–1108
Lüllmann-Rauch R (1975) Lipidosislike renal changes in rats treated with chlorphentermine or with tricyclic antidepressants. Virchows Arch (Cell Pathol) 18:51–60
Lullmann-Rauch R (1979) Drug-induced lysosomal storage disorders. In: Dingle JT, Jacques PJ, Shaw H (eds) Lysosomes in applied biology and therapeutics, vol. 6. North Holland, Amsterdam, pp 49–130
Lüllmann-Rauch R (1982) Histochemical evidence for lysosomal storage of acid glycosaminoglycans in splenic cells of rats treated with tilorone. Histochemistry 76:71–87
Lüllmann-Rauch R (1983) Tilorone-induced lysosomal storage mimicking the features of mucopolysaccharidosis and of lipidosis in rat liver. Virchows Arch (Cell Pathol) 44:355–368
Lüllmann-Rauch R (1986) Keratopathy in rats after treatment with tilorone. Graefe's Arch Clin Exp Ophthalmol 224:377–383
Murata K (1982) Glycosaminoglycans of kidney: normal and pathological aspects. In: Varma RS, Varma R (eds) Glycosaminoglycans and Proteoglycans in Physiological and Pathological Processes of Body Systems. Karger, Basel, pp 135–150
Pitcock JA, Leach BE, Rightsel WA, Muirhead EE (1978) Proteoglycans of the rat renal papillary interstitium, ultrastructural observations and synthesis by renomedullary intersitital cells. Fed Proc 37:633 (Abstr)
Regelson W (1981) The biological activity of the synthetic polyanion, pyran copolymer (Diveema; MVE, 46015) and the heterocyclic bis DEAE fluorenone derivative, tilorone and congeners: clinical and laboratory effects of these agents as modulators of host resistance. Pharmacol Ther 15:1–44
Scott JE, Dorling J (1965) Differential staining of acid glycosaminoglycans (mucopolysaccharides) by alcian blue in salt solutions. Histochemie 5:221–233
Shull RM, Helman RG, Spellacy E, Constantopoulos G, Munger RJ, Neufeld EF (1984) Morphologic and biochemical studies of canine mucopolysaccharidosis I. Am J Pathol 114:487–496
Spicer SS, Hardin JH, Setser ME (1978) Ultrastructural visualization of sulphated complex carbohydrates in blood and epithelial cells with the high iron diamine procedure. Histochem J 10:435–452
Thelmo WL, Levine S (1978) Renal lesions induced by tilorone and an analog. Am J Pathol 91:355–360
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lüllmann-Rauch, R. Lysosomal storage of sulfated glycosaminoglycans in renal interstitial cells of rats treated with tilorone. Cell Tissue Res. 250, 641–648 (1987). https://doi.org/10.1007/BF00218958
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00218958