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.

Proteolytic Activation Transforms Heparin Cofactor II into a Host Defense Molecule

“…2B). These results were similar to the bacterial destruction caused by membrane-acting antimicrobial peptides (12,14,15,22). Correspondingly, studies using the impermeant fluorescent probe FITC demonstrated that only HCIIa caused membrane permeabilization of bacterial cells (Fig.…”

“…For instance, although ATIII levels are reduced in almost all conditions associated with disseminated intravascular coagulation, reduced plasma levels of HCII are primarily detected during infection (8)(9)(10)(11). Increasing evidence pointing toward a close link between hemostasis, proteolysis, and host defense (12)(13)(14)(15)(16)(17) raised the hypothesis that HCII could play a role in host defense against infections.…”

A Novel Interaction between Complement Inhibitor C4b-binding Protein and Plasminogen That Enhances Plasminogen Activation

“…Complement has been shown to potentiate the coagulation cascade by inhibiting fibrinolysis, through C5a, which induces the expression of tissue factor and plasminogen-activator inhibitor 1 (37), whereas proteases of the coagulation and fibrinolytic system were shown to cleave and activate C3 and JULY 24, 2015 • VOLUME 290 • NUMBER 30 generate C5a (21,38). Additionally, during infections, localized complement-mediated coagulation activation enhances clotting, which not only provides a mechanical barrier against the spread of invading bacteria, but also helps in generating antimicrobial peptides and support the inflammatory response (21,39).…”

SufA – a novel subtilisin-like serine proteinase of Finegoldia magna

“…The pH was raised to 7.0 with 1 M Tris solution. Production of rabbit antibodies against a peptide of high-molecular-mass kininogen (NAT26) has been described (Frick et al, 2006).…”