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The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.

Abstract
The urinary tract functions in close proximity to the outside environment, yet must remain free of microbial colonization to avoid disease. The mechanisms for establishing an antimicrobial barrier in this area are not completely understood. Here, we describe the production and function of the cathelicidin antimicrobial peptides LL-37, its precursor hCAP-18 and its ortholog CRAMP in epithelial cells of human and mouse urinary tract, respectively. Bacterial contact with epithelial cells resulted in rapid production and secretion of the respective peptides, and in humans LL-37/hCAP-18 was released into urine. Epithelium-derived cathelicidin substantially contributed to the protection of the urinary tract against infection, as shown using CRAMP-deficient and neutrophil-depleted mice. In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract.
AuthorsMilan Chromek, Zuzana Slamová, Peter Bergman, László Kovács, L'udmila Podracká, Ingrid Ehrén, Tomas Hökfelt, Gudmundur H Gudmundsson, Richard L Gallo, Birgitta Agerberth, Annelie Brauner
JournalNature medicine (Nat Med) Vol. 12 Issue 6 Pg. 636-41 (Jun 2006) ISSN: 1078-8956 [Print] United States
PMID16751768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Cathelicidins
Topics
  • Animals
  • Anti-Infective Agents (pharmacology)
  • Antimicrobial Cationic Peptides (genetics, metabolism, pharmacology, urine)
  • Child
  • Drug Resistance, Bacterial
  • Epithelial Cells (cytology, metabolism, microbiology)
  • Escherichia coli (drug effects)
  • Escherichia coli Infections (immunology, microbiology, pathology)
  • Humans
  • Immunity, Mucosal
  • Kidney Cortex (cytology, metabolism, microbiology, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbial Sensitivity Tests
  • Neutrophils (metabolism)
  • Urinary Tract (drug effects, microbiology)
  • Urinary Tract Infections (immunology, microbiology, pathology)
  • Urothelium (cytology, metabolism, microbiology)
  • Cathelicidins

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