کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8463552 1549371 2018 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
LPS enhances platelets aggregation via TLR4, which is related to mitochondria damage caused by intracellular ROS, but not extracellular ROS
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
LPS enhances platelets aggregation via TLR4, which is related to mitochondria damage caused by intracellular ROS, but not extracellular ROS
چکیده انگلیسی
Platelet is an important cell contributing to hemostasis and immunity. Bacterial lipopolysaccharide (LPS), mainly functioning by stimulating toll-like receptor 4 (TLR4), mediates platelet activation and sepsis. However, the inter-relationship between these players in sepsis remains unknown. We found that the aggregation of platelets was enhanced in complete blood of sepsis patients than that of healthy donors. PRP isolated from complete blood of healthy donors was used in the following study to filter out the interference of irrelevant cells. The results shown that the maximum aggregation rate (MAR) was significantly higher in LPS-challenged PRP model than that of controls, and administration of the specific TLR4 inhibitor, TAK242, reduced the MAR in this model. LPS promoted P-selectin expression and intracellular ROS production, and both TAK242 and N-acetyl-L-cysteine (NAC) could depressed the LPS-induced increase of P-selectin and intracellular ROS. H2O2 administration increased P-selectin expression partially but had little effect on intracellular ROS, thought it increased mitochondrial damage. In vivo, LPS increased both intracellular ROS and CD62P comparing with that of controls, effects that were prevented by TAK242. Furthermore, platelet aggregation through LPS-TLR4 pathway was involved in AKT, PKC and p38 phosphorylation but not cGMP/cAMP pathway. In conclusion, this study shows that intracellular ROS, not extracellular ROS such as H2O2, plays a crucial role in facilitating platelet aggregation via LPS/TLR4 pathway, and this process was involved in AKT, PKC and p38 phosphorylation but not cGMP/cAMP pathway. The results would helpful for understanding the role of intracellular ROS and LPS-TLR4 pathway in platelet aggregation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Immunology - Volume 328, June 2018, Pages 86-92
نویسندگان
, , , , , ,