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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:e162.)
© 2004 American Heart Association, Inc.

Letters to the Editor

CD40L-Positive Platelets Induce CD40L Expression De Novo in Endothelial Cells: Adding a Loop to Microvascular Inflammation

Silvio Danese; Franco Scaldaferri; Alfredo Papa; Roberto Pola; Antonio Gasbarrini

Department of Internal Medicine, Catholic University, Rome, Italy

Allesandro Sgambato; Achille Cittadini

Institute of General Pathology, "Giovanni XXIII" Cancer Research Center, Catholic University, Rome, Italy

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

We read with great interest the article by Wagner et al, in which the authors elegantly showed that membrane bound CD154 (CD40 ligand [L]) expressed by T-cells can effectively trigger CD40L expression by endothelial cells. More importantly, the authors demonstrated a functional activity of endothelium-associated CD40L, thus revealing a novel costimulatory activity in monocyte–endothelial interactions.¹ We have recently performed a series of experiments that aimed to study CD40L induction by endothelial cells, in particular assessing the consequences of the interactions between CD40L positive platelets with CD40 bearing endothelial cells.

CD40L expression was evaluated by flow cytometry in human intestinal microvascular endothelial cells (HIMEC) cultured alone, with resting and thrombin activated platelets, or stimulated with different activators, including interleukin (IL)-1ß, tumor necrosis factor (TNF)-, and interferon (INF)-. Functional CD40–CD40L interactions were interrupted by using anti-CD40L specific antibodies, as reported.²

We found that CD40L was virtually absent in resting HIMEC (Figure A), and that all the potent proinflammatory molecules, such as IL-1ß, TNF-, and INF-, failed to induce CD40L expression, even though they were able to trigger HIMEC activation by upregulation of adhesion molecules (not shown). Resting platelets only slightly induced membrane bound endothelial CD40L (Figure B); in contrast, when endothelial cells were cultured with thrombin-positive CD40L platelets, HIMEC strongly upregulated CD40L expression (Figure C). Specificity of the CD40/CD40L pathway activation was demonstrated by platelet-CD40L blockade, as addressed by the strong inhibition induced by the use of the anti-CD40L antibodies (Figure . . . [Full Text of this Article]

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