Document Detail


Physiological relevance of LL-37 induced bladder inflammation and mast cells.
MedLine Citation:
PMID:  23313203     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells.
MATERIALS AND METHODS: To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients. LL-37 was measured by enzyme-linked immunosorbent assay. Our second hypothesis was tested in C57Bl/6 mice challenged with 7 LL-37 concentrations intravesically for 1 hour. At 24 hours tissues were examined histologically and myeloperoxidase assay was done to quantitate inflammation. In separate experiments fluorescent LL-37 was instilled and tissues were obtained immediately (time = 0) and at 24 hours (time = 24). To test our final hypothesis, we performed immunohistochemistry for mast cell tryptase and evaluated 5 high power fields per bladder to determine the mean number of mast cells per mm(2).
RESULTS: Urinary LL-37 was 89-fold higher in patients with spina bifida. Mouse LL-37 dose escalation experiments revealed increased inflammation at higher LL-37 concentrations. Fluorescent LL-37 demonstrated global urothelial binding at time = 0 but was not visible at time = 24. Immunohistochemistry for tryptase revealed mast cell infiltration in all tissue layers. At higher concentrations the LL-37 challenge led to significantly greater mast cell infiltration.
CONCLUSIONS: Urinary LL-37 was significantly increased in pediatric patients with spina bifida. To our knowledge we report for the first time that LL-37 can elicit profound, dose dependent bladder inflammation involving the urothelium. Finally, inflammation propagation involves mast cells.
Authors:
Siam Oottamasathien; Wanjian Jia; Lindsi McCoard Roundy; Jianxing Zhang; Li Wang; Xiangyang Ye; A Cameron Hill; Justin Savage; Wong Yong Lee; Ann Marie Hannon; Sylvia Milner; Glenn D Prestwich
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  The Journal of urology     Volume:  190     ISSN:  1527-3792     ISO Abbreviation:  J. Urol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-13     Completed Date:  2013-11-14     Revised Date:  2014-03-10    
Medline Journal Info:
Nlm Unique ID:  0376374     Medline TA:  J Urol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1596-602     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Animals
Antimicrobial Cationic Peptides / metabolism*,  toxicity
Cell Count
Child
Child, Preschool
Cystitis / etiology,  metabolism*,  pathology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immunohistochemistry
Infant
Infant, Newborn
Lipopolysaccharides
Male
Mast Cells / metabolism*,  pathology
Mice
Mice, Inbred C57BL
Spinal Dysraphism / complications,  metabolism*,  pathology
Urothelium / metabolism,  pathology
Grant Support
ID/Acronym/Agency:
NIH SBIR 1R43DK093413/DK/NIDDK NIH HHS; R43 DK093413/DK/NIDDK NIH HHS; UL1 RR025764/RR/NCRR NIH HHS; UL1RR025764/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Lipopolysaccharides; 143108-26-3/CAP18 lipopolysaccharide-binding protein
Comments/Corrections
Comment In:
J Urol. 2013 Oct;190(4 Suppl):1602   [PMID:  23792000 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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