Ambient fine particles (PM2.5) attenuate collagen-induced platelet activation through interference of the PLCγ2/Akt/GSK3β signaling pathway.

Autor: Yin, Zhao1, Xu, Hai‐Jiang1, Yao, Xia‐Li1, Liu, Gang2, Nie, Chun‐Jie1, Wei, Han1, Li, Cai1, Liang, Ming‐Lu3, Ming, Zhang‐Yin3 zyming@mail.hust.edu.cn, Zhang, Xiao‐Jian1 zhxj0524@sina.com
Předmět:
Zdroj: Environmental Toxicology. Feb2017, Vol. 32 Issue 2, p530-540. 11p.
Abstrakt: ABSTRACT Aims It has been proven that carbon nanoparticles or diesel exhaust particles stimulate platelet activation. However, the effect of fine particle matter (PM2.5) on platelet activation remains unknown, which motivates this study. Methods PM2.5 samples were collected in an urban area of Zhengzhou, China. To study the morphological characteristics and the mass concentrations of trace elements of PM2.5 samples, a filed-emission scanning electron microscope, the Image-J software, and an inductively coupled plasma mass spectrometry were used. Washed human platelets or platelet-rich-plasma were used to study the effect of PM2.5 on platelet aggregation, P-selectin expression, or platelet signaling pathways. The cytotoxicity in platelets exposed to PM2.5 was evaluated by a lactate dehydrogenase assay kit. In addition, platelet adhesion and spreading were studied on collagen-coated surfaces in stable conditions. Results The filed-emission scanning electron microscope scanning showed that PM2.5 samples varied in shape and size distributions. The mean equivalent spherical diameter of these particles was 1.97 ± 0.04 μm, of which 82.40% were particles with equivalent spherical diameters of less than 2.5 μm. The mass concentration of Ca was higher than that of other elements. The other elements followed the trend of Al>Fe>Zn>Mg>Pb>K>Mn>Cu>Ti>Ba>As>Sr>Sn>Sb>Cd>B>Se>Mo>Ag>Ni>TI>V>Co. Furthermore, pretreatment of PM2.5 significantly inhibited rather than potentiated collagen-induced platelet aggregation and P-selectin expression, whereas it had no significant effect on ADP-induced platelet aggregation and P-selectin expression. The lactate dehydrogenase analysis showed trivial cytotoxic effect of PM2.5 exposure on platelets. Pretreatment of PM2.5 inhibited platelet adhesion on immobilized collagen-coated surfaces; however, it almost did not impact the platelet spreading. Immunoblotting analysis indicated that PM2.5 reduced collagen-induced phosphorylation of phospholipase C gamma-2 (PLCγ2) at Tyr759, Akt at Ser473, and glycogen synthase kinase 3β (GSK3β) at Ser9. Conclusions PM2.5 attenuated collagen-induced platelet aggregation, α-granule secretion and adhesion, with the potential mechanism of impairing PLCγ2, Akt, and GSK3β signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 530-540, 2017. [ABSTRACT FROM AUTHOR]
Databáze: GreenFILE