TY - JOUR
T1 - Intravesical chondroitin sulfate inhibits recruitment of inflammatory cells in an acute acid damage "leaky bladder" model of cystitis
AU - Engles, Christopher D.
AU - Hauser, Paul J.
AU - Abdullah, Shivon N.
AU - Culkin, Daniel J.
AU - Hurst, Robert E.
N1 - Funding Information:
Funding Support: This work was supported in part by R01 DK069808 (REH) and by a grant from Stellar Pharmaceuticals, Inc.
Funding Information:
Financial Disclosures: R. E. Hurst has no financial interest other than as a recipient of the research grant from Stellar. No other authors have any financial interest. The chondroitin sulfate used for these studies was donated by Stellar Pharmaceuticals.
PY - 2012/2
Y1 - 2012/2
N2 - Objective: To investigate whether a physiologic effect of "glycosaminoglycan (GAG) replenishment therapy" altered recruitment of inflammatory cells in an acute bladder damage model. Replacement of the GAG layer with intravesically administered GAGs is an effective therapy for interstitial cystitis in at least some patients. Intravesically administered chondroitin sulfate was previously shown to bind to and restore the impermeability of surface-damaged ("leaky") urothelium to small ions. Methods: Rat bladders were damaged with 10 mM HCl. Negative control bladders were treated with phosphate-buffered saline. On the following day, the animal bladders were treated with 20 mg/mL chondroitin sulfate in phosphate-buffered saline, and the negative and positive controls were treated with phosphate-buffered saline alone. At 2 and 4 days after treatment with chondroitin sulfate, the rats were killed, and sections of their bladders were analyzed using toluidine blue staining for mast cell immunohistochemical labeling using antibodies against CD45 for lymphocytes and myeloperoxidase for neutrophils. Results: Chondroitin sulfate treatment reduced the recruitment, in a statistically significant manner, of inflammatory cells, including neutrophils and mast cells to the suburothelial space but did not alter recruitment of CD45-positive lymphocytes. Conclusion: For the first time, we have demonstrated that intravesical GAG replenishment therapy also produces a physiologic effect of decreasing recruitment of inflammatory cells in an acute model of the damaged bladder. These findings support the use of intravesically administered GAG for bladder disorders that result from a loss of impermeability, including interstitial, radiation, and chemical cystitis, and possibly others as well.
AB - Objective: To investigate whether a physiologic effect of "glycosaminoglycan (GAG) replenishment therapy" altered recruitment of inflammatory cells in an acute bladder damage model. Replacement of the GAG layer with intravesically administered GAGs is an effective therapy for interstitial cystitis in at least some patients. Intravesically administered chondroitin sulfate was previously shown to bind to and restore the impermeability of surface-damaged ("leaky") urothelium to small ions. Methods: Rat bladders were damaged with 10 mM HCl. Negative control bladders were treated with phosphate-buffered saline. On the following day, the animal bladders were treated with 20 mg/mL chondroitin sulfate in phosphate-buffered saline, and the negative and positive controls were treated with phosphate-buffered saline alone. At 2 and 4 days after treatment with chondroitin sulfate, the rats were killed, and sections of their bladders were analyzed using toluidine blue staining for mast cell immunohistochemical labeling using antibodies against CD45 for lymphocytes and myeloperoxidase for neutrophils. Results: Chondroitin sulfate treatment reduced the recruitment, in a statistically significant manner, of inflammatory cells, including neutrophils and mast cells to the suburothelial space but did not alter recruitment of CD45-positive lymphocytes. Conclusion: For the first time, we have demonstrated that intravesical GAG replenishment therapy also produces a physiologic effect of decreasing recruitment of inflammatory cells in an acute model of the damaged bladder. These findings support the use of intravesically administered GAG for bladder disorders that result from a loss of impermeability, including interstitial, radiation, and chemical cystitis, and possibly others as well.
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U2 - 10.1016/j.urology.2011.10.010
DO - 10.1016/j.urology.2011.10.010
M3 - Article
C2 - 22137543
AN - SCOPUS:84856722360
SN - 0090-4295
VL - 79
SP - 483.e13-483.e17
JO - Urology
JF - Urology
IS - 2
ER -