Figure 1.

Relevance of components of the kinin system in bacterial infections. (A) E. coli LPS is a classical stimulus for kinin B₁ receptor induction in vascular tissues, likely contributing to hypotension in systemic inflammation. E. coli LPS-induced B₁ receptor upregulation rely on TLR4 activation and de novo protein synthesis, mediated by the transcriptional factor NF-κB. Part of the hypotensive effects of LPS are related to an increased production of BK and B₂ receptor activation. (B) Streptococcal respiratory infections caused by S. pyogenes trigger the activation of contact system, via modulation of FXII, PPK and kallikrein. Plasmin activation by S. pyogenes streptokinase increases BK levels. Upon the bacteria spread throughout the blood stream due to increased vascular permeability, the patient develops systemic inflammatory response syndrome (SIRS) with coagulopathy and hypotension, causing multiple organ failure and shock. The modulation of one or more components of kinin formation pathways might be useful for management of septic patients. (C) P. gingivalis-produced gingipains cleave kininogen precursors, leading to BK and Lys-BK formation in periodontal tissues. Part of tissue destruction is mediated by the activation of constitutive B₂ receptors. P. gingivalis LPS activates TLR2 and induces an upregulation of B₁ receptors, which might sustain the chronic inflammation in periodontal disease. (D) M. tuberculosis infection is able to upregulate kinin B₁ receptors in lungs, with an increased formation of the selective B₁ receptor agonist, des-Arg⁹-BK from BK. Pharmacological inhibitors of B₁ receptors might be therapeutic adjuvants for reducing TB infection burden.