期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 16, 期 9, 页码 1843-1856出版社
WILEY
DOI: 10.1111/jth.14214
关键词
adhesion; anti-v3 autoantibody; immune thrombocytopenic purpura; megakaryocytes; migration
资金
- National Natural Science Foundation of China [81573084, 81502755]
- National Natural Science Funds for Distinguished Young Scholar [81725019]
- Program for Scientific and Technological Innovation Leader of Chongqing [CSTCKJCXLJRC06]
- China Postdoctoral Science Foundation [2014T70976]
- Natural Science Foundation of Chongqing [cstc2013jcyjA10119]
- Chongqing Postdoctoral Science Foundation [Xm201339]
Background The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. Anti-v3 integrin autoantibody is detected in chronic ITP patients, but its contribution to ITP is still unclear. Objectives To clarify the potential role of anti-v3 integrin autoantibody in chronic ITP and the related mechanism. Methods Relationship between levels of anti-v3 autoantibody and platelets in chronic ITP patients was evaluated. The influence of anti-v3 antibody on megakaryocyte (MK) survival, differentiation, migration and adhesion was assessed, and the associated signal pathways were investigated. Platelet recovery and MKs' distribution were observed in an ITP mouse model pretreated with different antibodies. Result In this study, we showed that the anti-v3 autoantibody usually coexists with anti-IIb3 autoantibody in chronic ITP patients, and patients with both autoantibodies have lower platelets. In invitro studies, we showed that the anti-v3 antibody had no significant effect on the survival and proliferation of MKs, whereas it decreased formations of proplatelet significantly. Anti-v3 antibody impeded stromal cell derived facor-1 alpha (SDF-1)- mediated migration and inhibited the phosphorylation of protein kinase B. Anti-v3 antibody significantly inhibited MKs' adhesion to endothelial cells and Fibrogen. The phosphorylation of focal adhesion kinase and proto-oncogene tyrosine-protein kinase Src induced by adhesion was inhibited when MKs were pretreated with anti-v3 antibody. In invivo studies, we showed that injection with anti-(v) antibody delayed platelet recovery in a mouse model of ITP. Conclusions These findings demonstrate that the autoantibody against integrin (v3) may aggravate thrombocytopenia in ITP patients by impeding MK migration and adhesion to the vascular niche, which provides new insights into the pathogenesis of ITP.
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