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Int. J. Mol. Sci. 2014, 15(12), 22342-22364;

The Signaling Role of CD40 Ligand in Platelet Biology and in Platelet Component Transfusion

Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France
French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne 42023, France
INSERMu1016, Institut Cochin, Departement "Infection, Immunity and Inflammation", Paris 75014, France
CNRS-UMR8104, Institut Cochin, Paris 75014, France
Université Paris-Descartes, Sorbonne Paris Cité, Paris 75270, France
Institut National de Transfusion Sanguine (INTS), Paris 75739, France
Authors to whom correspondence should be addressed.
Received: 30 October 2014 / Revised: 25 November 2014 / Accepted: 27 November 2014 / Published: 3 December 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
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The CD40 ligand (CD40L) is a transmembrane molecule of crucial interest in cell signaling in innate and adaptive immunity. It is expressed by a variety of cells, but mainly by activated T-lymphocytes and platelets. CD40L may be cleaved into a soluble form (sCD40L) that has a cytokine-like activity. Both forms bind to several receptors, including CD40. This interaction is necessary for the antigen specific immune response. Furthermore, CD40L and sCD40L are involved in inflammation and a panoply of immune related and vascular pathologies. Soluble CD40L is primarily produced by platelets after activation, degranulation and cleavage, which may present a problem for transfusion. Soluble CD40L is involved in adverse transfusion events including transfusion related acute lung injury (TRALI). Although platelet storage designed for transfusion occurs in sterile conditions, platelets are activated and release sCD40L without known agonists. Recently, proteomic studies identified signaling pathways activated in platelet concentrates. Soluble CD40L is a good candidate for platelet activation in an auto-amplification loop. In this review, we describe the immunomodulatory role of CD40L in physiological and pathological conditions. We will focus on the main signaling pathways activated by CD40L after binding to its different receptors. View Full-Text
Keywords: CD40 ligand; CD40; inflammation; signaling pathways; p38 mitogen-activated protein kinases (MAPK); nuclear factor-KappaB (NF-κB) CD40 ligand; CD40; inflammation; signaling pathways; p38 mitogen-activated protein kinases (MAPK); nuclear factor-KappaB (NF-κB)

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Aloui, C.; Prigent, A.; Sut, C.; Tariket, S.; Hamzeh-Cognasse, H.; Pozzetto, B.; Richard, Y.; Cognasse, F.; Laradi, S.; Garraud, O. The Signaling Role of CD40 Ligand in Platelet Biology and in Platelet Component Transfusion. Int. J. Mol. Sci. 2014, 15, 22342-22364.

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