Domain 5 of high molecular weight kininogen is antibacterial.

Research output: Contribution to journalArticle

Abstract

Antimicrobial peptides are important effectors of the innate immune system. These peptides belong to a multifunctional group of molecules that apart from their antibacterial activities also interact with mammalian cells and glycosaminoglycans and control chemotaxis, apoptosis, and angiogenesis. Here we demonstrate a novel antimicrobial activity of the heparin-binding and cell-binding domain 5 of high molecular weight kininogen. Antimicrobial epitopes of domain 5 were characterized by analysis of overlapping peptides. A peptide, HKH20 (His(479) - His(498)), efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and the Gram-positive Enterococcus faecalis. Fluorescence microscopy and electron microscopy demonstrated that HKH20 binds to and induces breaks in bacterial membranes. Furthermore, no discernible hemolysis or membrane-permeabilizing effects on eukaryotic cells were noted. Proteolytic degradation of high molecular weight kininogen by neutrophil-derived proteases as well as the metalloproteinase elastase from P. aeruginosa yielded fragments comprising HKH20 epitopes, indicating that kininogen-derived antibacterial peptides are released during proteolysis.

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Subject classification (UKÄ) – MANDATORY

  • Dermatology and Venereal Diseases
  • Other Clinical Medicine
  • Infectious Medicine
Original languageEnglish
Pages (from-to)34832-34839
JournalJournal of Biological Chemistry
Volume280
Issue number41
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes

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