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[Expression levels of CXCR4 on megakaryocytes and its ligand in bone marrow in children with acute idiopathic thrombocytopenic purpura]. | LitMetric

[Expression levels of CXCR4 on megakaryocytes and its ligand in bone marrow in children with acute idiopathic thrombocytopenic purpura].

Zhonghua Er Ke Za Zhi

Department of Pediatrics, the First Affiliated Hospital of Medical College, Zhengzhou University, Zhengzhou 450052, China.

Published: July 2004

AI Article Synopsis

  • The study investigates the role of the CXCR4 receptor and its ligand SDF-1alpha in megakaryocyte function and platelet production in children with immune thrombocytopenic purpura (ITP).
  • Findings show that children with ITP have significantly lower levels of CXCR4 and SDF-1alpha compared to healthy children, indicating a possible disruption in megakaryocyte maturation and platelet release.
  • After treatment with high-dose intravenous immunoglobulin (HDIVIgG), children responsive to the treatment show increased levels of CXCR4 and SDF-1alpha, suggesting a potential link between these factors and treatment efficacy.

Article Abstract

Objective: Chemokine receptor CXCR4 and its ligand stromal-derived factor 1 alpha (SDF-1alpha) have been paid increasing attention for their involvement in megakaryocytic hematopoiesis. It has been revealed in recent years that they can induce mature and immature megakaryocytes (MKs) to migrate through bone marrow endothelial cells (BMEC) by increasing the affinity of MKs for BMEC. Thus MKs maturity and eventual release of platelet from MKs ensues. While maturity disturbance of MKs and impaired production of platelets have been regarded as the main pathogenesis of ITP, the mechanism of which still remains unclear. Therefore, a clear understanding of the levels of CXCR4 and SDF-1alpha within bone marrow in children with ITP will help us to elucidate further the mechanism of ITP as well as to provide direct theoretical evidence for predicting treatment effect and evaluating prognosis.

Methods: Bone marrow were aspirated from 28 children with AITP and 12 normal children. Percoll density gradient and immunomagnetic beads method were used to purify megakaryocytes from the bone marrow. The immune cytochemistry was used to detect CXCR4 on megakaryocytes. The levels of SDF-1alpha were detected by ELISA. SPSS10.0 statistical software was used to deal with the experimental data.

Results: Before the treatment in children with AITP, both the CXCR4 expression on megakaryocytes and the SDF-1alpha level in bone marrow plasma were markedly decreased compared with the normal controls (P < 0.05). As to the cases who were sensitive to the high-dose intravenous immunoglobulin (HDIVIgG), the CXCR4 and SDF-1alpha levels were much higher in children after the treatment than those before the treatment (P < 0.05). In 6 cases insensitive to HDIVIgG, before the treatment the CXCR4 level was much lower than the children sensitive to HDIVIgG (P < 0.05).

Conclusions: The low levels of CXCR4/SDF-1alpha system in bone marrow may be one of the factors which contribute to the maturity disturbance of megakaryocytes and disturbance of platelets production in AITP, while decreased CXCR4/SDF-1alpha system may be caused by the effect of autoantibody against platelet. The mechanism of HDIVIgG in the treatment of AITP may involve in the increasing expression of CXCR4/SDF-1alpha system. The level of CXCR4 on megakaryocytes may play a certain role in predicting the treatment effect of immunoglobulin.

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