The effect of TLR4 expression in platelets and activation of platelets on the pathogenesis of thrombocytopenia induced by lipopolysaccharide in mice
- Author:
- No author available
- Journal Title:
- Chinese Journal of Emergency Medicine
- Issue:
- 12
- DOI:
- 10.3760/cma.j.issn.1671-0282.2011.12.017
- Key Word:
- 脂多糖;内毒素血症;血小板减少;血小板活化;Toll样受体4;巨噬细胞集落刺激因子;可溶性CD40配体;中性粒细胞;平均血小板体积;血小板分布宽度;Lipopolysaccharides;Endotoxemia;Thrombocytopenia;Platelet activation;Toll like receptor 4;Macrophage colony- stimulating factor;Soluble CD40 ligand;Neutrophils;Mean platelet volume;Platelet distribution width
Abstract： Objective To determine the role of the platelet activation and the expression of platelet Toll-like receptor 4 (TLR4) in thrombocytopenia induced by lipopolysaccharide (LPS) in mice.Methods ICR mice were randomly (random number) divided into control group,model 3,6,12,24,48,72h groups and neutrocytopenia syndrome (NEP) group.The blood samples of mice in model groups were detected 3,6,12,24,48,and 72 hours after intravenous injection of LPS respectively.Anti- neutrophil monoclonal antibody was administered in the mice of NEP group 24 h before injection of LPS,and blood samples were collected 24 h after injection of LPS.The determination of platelet count (PC),mean platelet volume (MPV) and platelet distribution width (PDW) was carried out with full automatic hemocyte analyzer.The plasma tumor necrosis factor- α (TNF- α),macrophage colony stimulating factor (M-CSF) and soluble CD40 ligand (sCD40L) levels were measured by using ELISA.The rate of platelet TLR4 expression was detected by flow cytometry.Comparison between groups was carried out by using ANOVA statistical methods.Results PC was reduced by 30％ 3 h after intravenous injection of LPS,and reached the lowest level within 24 h (P ＜0.01 ).MPV and PDW were increased compared with healthy controls (P ＜0.01 ).Plasma TNF - α,M - CSF and sCD40L were significantly increased after LPS stimulation (P ＜0.01 ),and reached the peak during 6 ～ 24 h after LPS administration.PC had correlation with plasma levels of M - CSF ( r =- 0.746) and sCD40L ( r =- 0.573 ).The platelet TLR4 expression was significantly increased 6 h after LPS stimulation.The platelet TLR4 expression in NEP group was significantly lower than that in 24 h model group ( P ＜ 0.01 ).Conclusions The excessive activation platelet represented by increase in sCD40L,MPV,PDW and high levels of M-CSF in macrophages along with platelet TLR4 expression participate in the pathogenesis of thrombocytopenia.The up - regulation of the platelet TLR4 expression is dependent on neutrophils in case of thrombocytopenia induced by LPS.
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