Summary
Investigations into the antibacterial defense mechanisms of the urinary tract revealed an important function for cell surface glycosaminoglycans (GAG), that of a generalized antiadherent activity. This activity was found to prevent bacterial, protein, and ionic adherence to the cell membrane. A model was developed to explain mechanically the activity of sulfated polysaccharides at the bladder surface. The model predicted injurious effects of quaternary amines and also that the mucus would be the so-called blood-urine barrier. It also led to the hypothesis that exogenous polysaccharides may be important in treating bladder disease such as infection and interstitial cystitis. For the first clinical test of these concepts, a polysaccharide was employed in several double-blind studies and was shown to ameliorate significantly the symptoms of interstitial cystitis. These discoveries suggest new methods to manipulate the microenvironment between the transitional cell surface and the urine, leading to novel therapies in regulating disease of the genitourinary tract. They also stress the importance of understanding the mechanisms by which GAGs exert their effect in the urinary tract and how they are produced, maintained, and even inactivated (e.g., by urinary substances such as protamine).
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References
Anderstrom CR, Fall M, Johansson SL (1989) Scanning electron microscopic findings in interstitial cystitis. Br J Urol 63:270–275
Dixon JS, Holm-Bentzen M, Gilpin CJ, Gosling JA, Bostofte E, Hald T, Larsen S (1986) Electron microscopic investigation of the bladder urothelium and glycocalyx in patients with interstitial cystitis. J Urol 135:621–625
Eldrup J, Thorup J, Nielsen SL, Hald T, Hainau B (1983) Permeability and ultrastructure of human bladder epithelium. Br J Urol 55:488–492
Felsen D, Frye S, Bavendam TG, Parsons CL, Trimble LA, Vaughan ED (1993) Urinary imflammatory mediator profiles in interstitial cystitis (IC) patients, patients with IC-like symptoms, and controls (abstract). J Urol 149:507A
Gill WG, Jones KW, Ruggiero KJ (1982) Protective effects of heparin and other sulfated glycosaminoglycans on crystal adhesion to injured urothelium. J Urol 127:152–154
Gregor HP (1976) Fixed-charge ultrafiltration membranes. In: Selegny E (ed) Charged gels and membranes, vol I. D. Reidel, p 235
Gregor HP (1976) Anticoagulant activity of sulfonate polymers and copolymers. In: Gregor HP (ed) Polymer science and technology, vol 5. Plenum, New York p 51
Gryte CC, Gregor HP (1976) Poly(styrene sulfonic acid)-poly-(vinylidene fluoride) interpolymer ion-exchange membranes. J Polymer Sci 14:1839–1854
Hanno P, Levin RM, Monson FC, Teuscher C, Zhou ZZ, Ruggieri M, Whitmore K, Wein AJ (1990) Diagnosis of interstitial cystitis. J Urol 143:278–281
Hanno P, Parsons CL, Shrom S, Fritz R, Mulholland S (1978) The protective effect of intravesical heparin in experimental bladder infection. J Surg Res 25:324–329
Hohlbrugger G, Lentsch P (1985) Intravesical ions, osmolality and pH influence the volume pressure response in the normal rat bladder, and this is more pronounced after DMSO exposure. Eur Urol 11:127–130
Holm-Bentzen M, Jacobsen F, Nerstrom B, Lose G, Kristensen JK, Pedersen RH, Krarup T, Feggetter J, Bates P, Barnard R, Larsen S, Hald T (1987) Painful bladder disease: clinical and pathoanatomical differences in 115 patients. J Urol 138:500–502
Holm-Bentzen M, Lose G (1987) Pathology and pathogenesis of interstitial cystitis. Urology 29 [Suppl 4]:8–13
Hurst RE (1978) Thermodynamics of the partition of chondroitin sulfate-hexadecylpyridinium complexes in butanol/aqueous salt biphasic solutions. Biopolymers 17:2601–2608
Hurst RE, Jennings GC, Lorincz AE (1977) Partition techniques for isolation and fractionation of urinary glycosaminoglycans. Anal Biochem 79:502–512
Hurst RE, Rhodes SW, Adamson PB, Parsons CL, Roy JB (1987) Functional and structural characteristics of the glycosaminoglycans of the bladder luminal surface. J Urol 138:433–437
Lilly JD, Parsons CL (1990) Bladder surface glycosaminoglycans: a human epithelial permeability barrier. Surg Gynecol Obstet 171:493–496
Lynes WL, Flynn SD, Shortliffe LD, Lemmers M, Zipser R, Roberts LJ II, Stamey TA (1987) Mast cell involvement in interstitial cystitis. J Urol 138:746–752
MacDermott JP, Miller CH, Levy N, Stone AR (1991) Cellular immunity in interstitial cystitis. J Urol 145:274–279
Menter JM, Hurst RE, Nakamura N, West SS (1979) Thermodynamics and cooperative parameters of acridine orange-heparin system. Biopolymers 18:493–505
Mulholland SG, Hanno P, Parsons CL, Sant GR, Staskin DR (1990) Pentosan polysulfate sodium for therapy of interstitial cystitis: a double-blind placebo-controlled clinical study. Urology 35:552–558
Niku SD, Stein PC, Scherz HC, Parsons CL (in press) A new method for cyto-destruction of bladder epithelium using protamine sulfate and urea. J Urol
Oravisto KJ (1990) Interstitial cystitis as an autoimmune disease. A review. Eur Urol 6:10–13
Parsons CL (1982) Prevention of urinary tract infection by the exogenous glycosaminoglycan sodium pentosanpolysulfate. J Urol 127:167–169
Parsons CL, Benson G, Childs SJ, Hanno P, Sant GR, Webster G (in press) A quantitatively controlled method to study prospectively interstitial cystitis and that demonstrates the efficacy of pentosanpolysulfate. J Urol 150
Parsons CL, Boychuk D, Jones S, Hurst R, Callahan H (1990) Bladder surface glycosaminoglycans: an epithelial permeability barrier. J Urol 143:139–142
Parsons CL, Greenspan C, Moore SW, Mulholland SG (1977) Role of surface mucin in primary antibacterial defense of the bladder. Urology 9:48–52
Parsons CL, Greenspan C, Mulholland S (1975) The primary antibacterial defense mechanism of the bladder. Invest Urol 13:72–76
Parsons CL, Lilly JD, Stein P (1991) Epithelial dysfunction in non-bacterial cystitis (interstitial cystitis). J Urol 145:732–735
Parsons CL, Pollen J, Anwar H, Stauffer C, Schmidt JD (1980) Antibacterial activity of bladder surface mucin duplicated in the rabbit bladder by exogenous glycosaminoglycan (sodium pentosanpolysulfate). Infect Immun 27:876–881
Parsons CL, Schmidt JD, Pollen J (1983) Successful treatment of interstitial cystitis with sodium pentosanpolysulfate. J Urol 130:51–53
Parsons CL, Stauffer C, Schmidt JD (1980) Bladder surface glycosaminoglycans: an efficient mechanism of environmental adaptation. Science 208:605–607
Parsons CL, Stauffer C, Schmidt JD (1981) Impairment of antibacterial effect of bladder surface mucin by protamine sulfate. J Infect Dis 144:180
Parsons CL, Stauffer CW, Schmidt JD (1988) Reversible inactivation of bladder surface glycosaminoglycan antibacterial activity by protamine sulfate. Infect Immun 56:1341–1343
Parsons CL, Stein PC, Bidair M, Lebow D (in press) Abnormal sensitivity to intravesical potassium in interstitial cystitis. Neurourol Urody
Uehling DT, Mizutani K, Balish E (1980) Inhibitors of bacterial adherence to urothelium. Invest Urol 18:40–42
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Supported by the Medical Research Service of the Veterans Administration, Urological Research and Education Foundation, and by National Institutes of Health grant R01DK39239.
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Parsons, C.L. A model for the function of glycosaminoglycans in the urinary tract. World J Urol 12, 38–42 (1994). https://doi.org/10.1007/BF00182049
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DOI: https://doi.org/10.1007/BF00182049