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题名:The contact system?—a novel branch of innate immunity generating antibacterial peptides
作者:Inga-Maria Frick, Per ?…kesson, Heiko Herwald, Matthias M??rgelin, Martin Malmsten, ...
来源:The EMBO Journal (09 Nov 2006) Article
URL :http://dx.doi.org/10.1038/sj.emboj.7601422
日期:061130
摘要:Inga-Maria Frick1, Per ?kesson1, Heiko Herwald1, Matthias M?rgelin1, Martin Malmsten2, Dorit K N?gler3 and Lars Bj?rck1

1 Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden
2 Department of Pharmacy, Uppsala University, Uppsala, Sweden
3 Department of Clinical Chemistry and Clinical Biochemistry, University Hospital of Surgery-City, Ludwig-Maximilians-University, Munich, Germany

To whom correspondence should be addressed
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


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.

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