Article
- The EMBO Journal (2006) 25, 5569 - 5578
- doi:10.1038/sj.emboj.7601422
Published online: 9 November 2006
Subject Category:
The contact system—a novel branch of innate immunity generating antibacterial peptides
Inga-Maria Frick1, Per Åkesson1, Heiko Herwald1, Matthias Mörgelin1, Martin Malmsten2, Dorit K Nägler3 and Lars Björck1
- Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden
- Department of Pharmacy, Uppsala University, Uppsala, Sweden
- Department of Clinical Chemistry and Clinical Biochemistry, University Hospital of Surgery-City, Ludwig-Maximilians-University, Munich, Germany
Correspondence to:
Inga-Maria Frick, Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, BMC, B14, S-221 84 Lund, Sweden. Tel.: +46 46 2228569; Fax: +46 46 157756; E-mail: Inga-Maria.Frick@med.lu.se
Received 28 June 2006; Accepted 12 October 2006
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.
Keywords:
- antibacterial peptides,
- bacterial killing,
- contact system,
- innate immunity
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