Domain 5 of high molecular weight kininogen is antibacterial.
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.
Nordahl
Emma Andersson
EA
Section of Dermatology and Venereology, Department of Clinical Sciences, Lund, Biomedical Center, Lund University, Tornavägen 10, SE-221 84 Lund, Sweden. emma.nordahl@med.lu.se
Rydengård
Victoria
V
Mörgelin
Matthias
M
Schmidtchen
Artur
A
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D002633:Chemotaxis; D004058:Diffusion; D013293:Enterococcus faecalis / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D006025:Glycosaminoglycans; D006090:Gram-Negative Bacteria; D006461:Hemolysis; D006493:Heparin / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D019679:Kininogen, High-Molecular-Weight / Q000737:chemistry*; D007704:Kininogens / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D009504:Neutrophils / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D000939:Epitopes; D006025:Glycosaminoglycans; D019679:Kininogen, High-Molecular-Weight; D007704:Kininogens; D010455:Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; D006493:Heparin; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue