Airborne Fine Particles Induce Hematological Effects through Regulating the Crosstalk of the Kallikrein-Kinin, Complement, and Coagulation Systems

Particulate air pollution caused by human activities has drawn global attention due to its potential health risks. Considering the inevitable contact of inhaled airborne fine particulate matter (PM) with plasma, the hematological effects of PM are worthy of study. In this study, the potential effect of PM on hematological homeostasis through triggering the crosstalk of the kallikrein-kinin system (KKS), complement, and coagulation systems in plasma was investigated. The ex vivo, in vitro, and in vivo KKS activation assays confirmed that PM samples could efficiently cause the cascade activation of key zymogens in the KKS, wherein the particles coupled with lipopolysaccharide attachment provided substantial contribution. The binding of Hageman factor XII (FXII) with PM samples and its subsequent autoactivation initiated this process. The crucial elements in the complement cascade, including complement (C3) and complement 5 (C5), and coagulation system (prothrombin) were also found to be actively induced by PM exposure, which was regulated by the interplay of KKS activation. The data provided solid evidence on hematological effects of airborne PM through inducing the activation of the KKS, complement, and coagulation systems, which would be valuable in the risk assessment on air-pollution-related cardiovascular diseases.