955 INTRAVESICAL CHONDROITIN SULFATE INHIBITS RECRUITMENT OF INFLAMMATORY CELLS TO A “LEAKY” BLADDER

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2011955 INTRAVESICAL CHONDROITIN SULFATE INHIBITS RECRUITMENT OF INFLAMMATORY CELLS TO A “LEAKY” BLADDER Robert Hurst, Christopher Engles, Paul Hauser, and Daniel Culkin Robert HurstRobert Hurst Oklahoma City, OK More articles by this author , Christopher EnglesChristopher Engles Oklahoma City, OK More articles by this author , Paul HauserPaul Hauser Oklahoma City, OK More articles by this author , and Daniel CulkinDaniel Culkin Oklahoma City, OK More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.900AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Replacement of the glycosaminoglycan (GAG) layer with intravesically-administered GAGs such as heparin, chondroitin sulfate (ChS) or pentosan polysulfate has proven to be an effective therapy for interstitial cystitis. Previous studies have shown that intravesical chondroitin sulfate binds to and restores the impermeability of surface-damaged (“leaky”) urothelium to small ions. This study determined whether therapeutic replacement of the GAG layer in surface-damaged bladder produced a physiologic effect on recruitment of inflammatory cells. METHODS Rat bladders were treated by instillation of 400 μL of 10mM HCl in 0.154 M NaCl through a cannula that was surgically implanted into the dome of the rat bladder. Negative control bladders were injected with 400 μL of PBS. On the following day, the animal bladders were treated with 400 μL of 20mg/mL chondroitin sulfate in 0.154M NaCl, while the negative and positive controls were treated with 400 μL of PBS alone. Two and four days after treatment with chondroitin sulfate, animals were euthanized, and sections of their bladders analyzed by immunohistochemical labeling using antibodies against CD-45 (lymphocytes), myeloperoxidase (neutrophils) and Toluidine Blue (mast cells). RESULTS Control values showed 17.3 ± 9.8 neutrophils (myeloperoxidase-positive) per section which increased to 119.5 ± on day 2 and 190.5 ± 103.9 on day 4. When treated with ChS, the number of neutrophils was reduced to 70.9 ± 49.7 (41%)(p=0.107) and 124.5 ± 64.0 (33%)(p=0.042). The effect on mast cells was similar. Without ChS, the number of mast cells (Toluidine Blue-positive) per section increased from 28.6 ± 14.4 to 98.3 ± 47.3 on day 2 to 159.7 ± 43.1 on day 4. ChS treatment reduced these to 62.4 ± 26.5 (37%) on day 2 (P=0.014) and to 91.9 ± 34.5 (42%) (p=0.00005) on day 4. No differences in lymphocytes (CD45-positive cells were observed). CONCLUSIONS In the absence of treatment, neutrophils increased 7- and 11-fold 2 and 4 days following removal of the protective “umbrella cells,' and mast cells increased 4- and 6-fold respectively. Treatment of damaged bladder with chondroitin sulfate inhibited the recruitment of inflammatory cells to the detrusor underlying bladder damage by about 40% at day 2 and day 4. Restoration of the GAG layer therefore is effective in reducing the cellular inflammatory response resulting from leakage at the urothelium. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e384 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Robert Hurst Oklahoma City, OK More articles by this author Christopher Engles Oklahoma City, OK More articles by this author Paul Hauser Oklahoma City, OK More articles by this author Daniel Culkin Oklahoma City, OK More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...