CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells

Abstract

CD40 ligand (CD40L, CD154), a transmembrane protein structurally related to the cytokine TNF-α, was originally identified on stimulated CD4+ T cells1,2,3, and later on stimulated mast cells and basophils4. Interaction of CD40L on T cells with CD40 on B cells is of paramount importance for the development and function of the humoral immune system5. CD40 is not only constitutively present on B cells, but it is also found on monocytes, macrophages and endothelial cells, suggesting that CD40L has a broader function in vivo. We now report that platelets express CD40L within seconds of activation in vitro and in the process of thrombus formation in vivo. Like TNF-α and interleukin-1, CD40L on platelets induces endothelial cells to secrete chemokines and to express adhesion molecules, thereby generating signals for the recruitment and extravasation of leukocytes at the site of injury. Our results indicate that platelets are not only involved in haemostasis but that they also directly initiate an inflammatory response of the vessel wall.

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Figure 1: Expression of CD40L on activated platelets.
Figure 2: CD40L on platelets has the same structure and specificity as CD40L on activated CD4+ T cells.
Figure 3: CD40L on activated platelets induces endothelial cells to express E-selectin, VCAM-1 and ICAM-1.
Figure 4: CD40L on activated platelets co-induces endothelial cells to secrete IL-8 and MCP-1.
Figure 5: Expression of CD40L on activated platelets in vivo.

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Acknowledgements

J.R.S. is a postdoctoral fellow of the Max-Planck Society. We thank R. Kurrle for the generous gift of CD40-Ig, J. Schröder for ELISA reagents for determination of IL-8, and H.W. Mages for critically reading the manuscript.

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Correspondence to Richard A. Kroczek.

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Henn, V., Slupsky, J., Gräfe, M. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391, 591–594 (1998). https://doi.org/10.1038/35393

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