The Plasma Kallikrein-Kinin System: A Hematological Target for Environmental Contaminants

The increasing occurrence of emerging chemicals of concern in the environment has caused high public attention. Assessing their hematologic toxicities is of high priority, as the blood circulation system is usually essential in transporting these exogenous substances to diverse target tissues in vivo. The plasma kallikrein-kinin system (KKS) is one of the most abundant protease enzyme systems and regulates a series of crucial hematologic functions. As a vulnerable target, the KKS may sensitively respond to circulatory pollutants, and combing the current studies on the interaction of the environmental contaminants with the KKS would help understand the toxicological or pathological significance of this system. The current studies have revealed that some environmental contaminants, such as small molecular organic chemicals, engineered nanoparticles (NPs), and atmospheric fine particulate matter (PM), can directly interact with the KKS, causing the autoactivation of the Hageman factor XII (FXII), the subsequent cascade cleavage of the plasma prekallikrein (PPK), and high molecular kininogen (HK). The consequent downstream hematological effects and other related toxicities can be concomitantly induced via the crosstalk with the KKS. In addition, multiple approaches, based on in vitro, ex vivo, and in vivo experimental models, have been developed to characterize the binding of exogenous substances with FXII, conformational changes of the protein, the cascade activation of the KKS, and downstream toxicological or pathological responses. As a vulnerable target, the plasma KKS sensitively responds to the exposure of environmental pollutants and is promising for biomonitoring hematotoxicity in future studies.