MP24-10 DIABETIC CONDITIONS IMPAIR NEUTROPHIL RECRUITMENT INTO THE UROTHELIUM AND MARKEDLY DELAY THE CLEARANCE OF INTRACELLULAR BACTERIAL COMMUNITY OF UROPATHOGENIC E. COLI

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2016MP24-10 DIABETIC CONDITIONS IMPAIR NEUTROPHIL RECRUITMENT INTO THE UROTHELIUM AND MARKEDLY DELAY THE CLEARANCE OF INTRACELLULAR BACTERIAL COMMUNITY OF UROPATHOGENIC E. COLI Yan Liu, Feng He, Ellen Shapiro, Herbert Lepor, and Xue-Ru Wu Yan LiuYan Liu More articles by this author , Feng HeFeng He More articles by this author , Ellen ShapiroEllen Shapiro More articles by this author , Herbert LeporHerbert Lepor More articles by this author , and Xue-Ru WuXue-Ru Wu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.766AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diabetes mellitus (DM) is often associated with an increased risk of urinary tract infection, but the underlying mechanisms, particularly those at the pathogen-host interface, i.e., the urinary tract, remain unclear. In this study, we examined whether experimental DM in mice affects neutrophil infiltration into and clearance of uropathogenic E. coli from the urothelium. METHODS Female mice (C57BL/6, 9 weeks) were injected intraperitoneally with streptozotocin (STZ) at 200 mg/kg. Blood glucose level was measured daily until it reached a plateau by day 3. On day 7, normal and STZ-induced DM mice were challenged by transurethral inoculation of uropathogenic E. coli strain UTI89. The extent of neutrophil infiltration in the urothelium was assessed using confocal immunofluorescence microscopy (CIM) and urine neutrophil elastase activity assay. The presence of intracellular bacterial community (IBC) formed by UTI89 was assessed at 12 hours, 24 hours, 3 days and 7 days post-UTI89 inoculation with CIM using an anti-E. coli antibody and bacterial culture. Functional defects in neutrophil migration were verified using in vitro migration assays of peripheral blood neutrophils. RESULTS Hyperglycemia (440-470 mg/dl) was induced reproducibly and permanently in all the mice administered with STZ with little inter-animal variation. Normal controls and STZ-induced DM mice transurethrally inoculated with UTI89 showed marked differences in neutrophil infiltration at all time points examined. While in normal mice neutrophils that infiltrated into the urothelium were most frequently seen surrounding IBCs, in STZ mice the neutrophils were very sparse and scattered. There was a 2-fold reduction of neutrophil elastase at 12 hours post-inoculation in STZ mice than in the normal controls. In contrast, IBCs were considerably more prevalent in STZ mice at 12 and 24 hours post-inoculation. On day 3 and 7 when few IBCs remained in normal mouse urothelium, numerous IBCs were seen in the STZ mice, often lining the entire segment of superficial urothelium. Bacterial culture confirmed the IBC staining data. Finally, in vitro assay showed that neutrophils from the STZ mice were three-fold less migratory than those from the normal mice. CONCLUSIONS Our data provide the first experimental evidence indicating that diabetic conditions impair neutrophil migration and infiltration into the urothelium, resulting in markedly delayed host responses in IBC clearance and consequently prolonged bladder infection. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e273-e274 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yan Liu More articles by this author Feng He More articles by this author Ellen Shapiro More articles by this author Herbert Lepor More articles by this author Xue-Ru Wu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...