Kinin cascade/system

Interaction with Other Cascade Systems. Interactions between the complement system, the kinin, and the coagulation and fibrinolytic systems have repeatedly been reported (S37, PI9). Activation of one system induces activation of the other systems. The reciprocal activation of the various cascade systems may have an important role in the pathogenesis of ARDS and MODS as complications of sepsis. Nevertheless, until now no convincing prophylactic or therapeutic effects of intervention in the complement cascade system on the severity of septic complications have been reported. 

As a result of the contact of blood with none-ndothelial surfaces, several humoral and cellular systems can be activated. Exposure of blood proteins and cells to blood contacting medical devices can activate plasma proteolytic systems (coagulation (blood clotting system), fibrinolysis (process by which clot is broken down), complement cascade (a system of soluble proteins involved in microbiocidal activity and the release of inflammatory components), Kallekrein-kinin and contact systems) and at least three cellular elements (leukocytes, endothelial cells, and platelets). Contrary to the normal situations whereby these mechanisms are localized and intended to promote wound healing, activation of these systems by medical devices can result in nonlocalized systemic reactions. The preclinical and clinical assessments of hemocompatibility are designed to minimize modification of these systems. 

We demonstrated that BK is an important mediator of EPR effect in cancer [36]. Figure 5 shows network of BK and other mediators involving in EPR effect. BK interacts with various proinflammatory factors involving vascular permeability. For instance, it is also known to activate endothelial cell-type nitric oxide synthase (eNOS), which is one of the primary enzymes to produce NO from L-arginine. We have reported that the BK-generating cascade is activated in tumor tissues [36]. More importantly, malignant ascetic and pleural fluids would be caused by activation of kallikrein-kinin system in carcinomatosis [37]. 

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