title: The contact system--a novel branch of innate immunity generating antibacterial peptides.
abstract: Activation of the contact system has two classical consequences: initiation of the intrinsic pathway of coagulation, and cleavage of high molecular weight kininogen (HK) leading to the release of bradykinin, a potent proinflammatory peptide. In human plasma, activation of the contact system at the surface of significant bacterial pathogens was found to result in further HK processing and bacterial killing. A fragment comprising the D3 domain of HK is generated, and within this fragment a sequence of 26 amino acids is mainly responsible for the antibacterial activity. A synthetic peptide covering this sequence kills several bacterial species, also at physiological salt concentration, as effectively as the classical human antibacterial peptide LL-37. Moreover, in an animal model of infection, inhibition of the contact system promotes bacterial dissemination and growth. These data identify a novel and important role for the contact system in the defence against invasive bacterial infection.
authors.affiliation: Department of Clinical Sciences, Lund University, Sweden, and Department of Clinical Chemistry and Clinical Biochemistry, University Hospital of Surgery-City, Ludwig-Maximilians-University, Munich, Germany. Inga-Maria.Frick@med.lu.se
authors.forename: Inga-Maria
authors.initials: IM
authors.lastname: Frick
authors.forename: Per
authors.initials: P
authors.lastname: Akesson
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
authors.forename: Dorit K
authors.initials: DK
authors.lastname: Nägler
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate; D019679:Kininogen, High-Molecular-Weight / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary
chemical_list: D000900:Anti-Bacterial Agents; D019679:Kininogen, High-Molecular-Weight; D010455:Peptides