Abstract 992: Platelet-Associated LIGHT (TNFSF14) Mediates Adhesion of Activated Platelets to Human Vascular Endothelium
LIGHT (TNFSF 14) belongs to the tumor necrosis factor superfamily and is expressed by different types of immune cells. LIGHT binds to its cellular receptors herpes virus entry mediator (HVEM/TR2) and lymphotoxin beta receptor (LTβR) which are expressed also on vascular endothelial cells. Activation of endothelial cells by recombinant LIGHT results in pro-inflammatory and pro-thrombotic changes quantitatively comparable to effects of CD40 ligand. Given the important role of platelet-associated CD40 ligand in vascular inflammatory responses we investigated the role of LIGHT in adhesion of platelets on activated human endothelial cells. Adhesion experiments were recorded on videotape and evaluated off-line using Capimage software and direct phase contrast microscopy, respectively. Surface expression of LIGHT on ADP or TRAP-1 activated but not resting platelets was confirmed by FACS analysis. Membrane-bound LIGHT on platelets contributes significantly to the rolling and firm adhesion of platelets that occurs under static and dynamic flow conditions on stimulated endothelial cells. Static as well as dynamic adhesion was reduced by ca. 40% using anti-LIGHT antibody compared to control IgG antibody. Surface expression of LIGHT upon various modes of activation was accompanied by secretion of soluble LIGHT (up to 20 pg/ml) into the supernatant as analyzed by ELISA. Plasma levels of soluble LIGHT were significantly higher in patients with myocardial infarction (NSTEMI, n=10 or STEMI, n=20) compared with 15 healthy controls (64.2+− 30.9 pg/ml vs. 24.8+−9.3 pg/ml, p<0.05). We propose a potential role of LIGHT in the development and progression of atherosclerotic lesions and atherothrombosis via platelet-endothelium adhesion. Soluble LIGHT of undetermined cellular source is detectable in serum of healthy controls, elevated levels are found in acute coronary syndrome.