Do CD40L and CD40 Contribute to Sickle Cell Anemia? Public Deposited

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  • March 21, 2019
  • Yeboah, Sybil A.
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
  • CD40 ligand (CD40L) is an important inflammatory mediator upregulated in inflammatory conditions such as atherosclerosis and sickle cell anemia (SCA). CD40L is expressed on platelets, B cells and epithelial cells, with platelets being its main source. Interaction with its receptor, CD40, has been shown to upregulate adhesion molecule expression, stimulate release of inflammatory molecules and initiate coagulation. These manifestations are also observed in SCA. Previously, our lab reported that the concentration of soluble CD40L ligand in sickle cell patient plasma is 30-fold higher than plasma of normal individuals. Based on these observations, we hypothesize that CD40L and CD40 contribute to SCA by increasing inflammation and blood cell adhesion to the endothelium. To test this hypothesis, we will block the CD40L:CD40 interaction a mouse model of SCA using an anti-CD40L antibody and analyze the effects on lung, liver, spleen and kidney pathology. Furthermore, we will also determine whether this blockade decreases expression of inflammatory mediators such as IL 8 and CD40L. These studies will help to further understand the role of the CD40L:CD40 interaction in SCA, and may eventually help to enhance the overall health of SCA individuals.
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  • Parise, Leslie
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