Frick Inga-Maria, Akesson Per, Herwald Heiko, Mörgelin Matthias, Malmsten Martin, Nägler Dorit K, Björck Lars
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.
EMBO J. 2006 Nov 29;25(23):5569-78. doi: 10.1038/sj.emboj.7601422. Epub 2006 Nov 9.
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.
启动凝血的内源性途径，以及裂解高分子量激肽原（HK）导致缓激肽释放，缓激肽是一种强效促炎肽。在人血浆中，发现重要细菌病原体表面的接触系统激活会导致HK的进一步加工和细菌杀伤。产生了一个包含HK的D3结构域的片段，在这个片段中，26个氨基酸的序列主要负责抗菌活性。覆盖该序列的合成肽在生理盐浓度下也能像经典的人类抗菌肽LL-37一样有效地杀死几种细菌。此外，在感染的动物模型中，接触系统的抑制会促进细菌的传播和生长。这些数据确定了接触系统在抵御侵袭性细菌感染中的新的重要作用。
