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

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Abstract

Purpose of Review

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.

Recent Findings

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.

Summary

As a vulnerable target, the plasma KKS sensitively responds to the exposure of environmental pollutants and is promising for biomonitoring hematotoxicity in future studies.

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Data Availability

The data reported in this review paper are based on raw data available in the published literature.

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Funding

This study was financially supported by the National Key R&D Program of China (2023YFC3706603) and the National Natural Science Foundation of China (22176203, 22176204, 22193053).

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Authors and Affiliations

  1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China

    Yurou Gao, Yuzhu Zhang, Zhiwen Li, Qian S. Liu, Qunfang Zhou & Guibin Jiang

  2. Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 100049, China

    Yurou Gao & Zhiwen Li

  3. School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310000, China

    Qunfang Zhou & Guibin Jiang

  4. Institute of Environment and Health, Jianghan University, Wuhan, 430056, China

    Qunfang Zhou

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Contributions

YR.G.: Conceptualization, Investigation, Methodology, Visualization, Writing original draft; Writing review & editing; YZ.Z.: Investigation, Writing review & editing; ZW.L.: Investigation, Writing review & editing; QS.L.: Supervision, Writing review & editing; QF.Z.: Conceptualization, Resources, Funding acquisition, Supervision, Writing review & editing; GB.J.: Resources, Project administration. All authors reviewed the manuscript.

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Correspondence to Qunfang Zhou.

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Gao, Y., Zhang, Y., Li, Z. et al. The Plasma Kallikrein-Kinin System: A Hematological Target for Environmental Contaminants. Curr Pollution Rep (2024). https://doi.org/10.1007/s40726-024-00308-8

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