gp91phox-dependent expression of platelet CD40 ligand

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-09, Vol.110 (10), p.1326-1329
• Main Authors: Pignatelli, P, Sanguigni, V, Lenti, L, Ferro, D, Finocchi, A, Rossi, P, Violi, F
• Format: Article
• Language: English
• Subjects: Adult; Antioxidants - pharmacology; Arachidonic Acid - metabolism; Arachidonic Acids - pharmacology; Aspirin - pharmacology; Blood Platelets - drug effects; Blood Platelets - metabolism; Catalase - pharmacology; CD40 Ligand - biosynthesis; CD40 Ligand - blood; CD40 Ligand - genetics; Collagen - pharmacology; Granulomatous Disease, Chronic - blood; Granulomatous Disease, Chronic - enzymology; Humans; Male; Mannitol - pharmacology; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; NADPH Oxidase 2; NADPH Oxidases - deficiency; NADPH Oxidases - genetics; NADPH Oxidases - physiology; Phospholipases A - antagonists & inhibitors; Phospholipases A2; Platelet Activation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Reactive Oxygen Species - metabolism; Superoxide Dismutase - pharmacology; Superoxides - metabolism; Thrombin - pharmacology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000134963.77201.55

CD40 ligand (CD40L) expression on platelets is mediated by agonists, but the underlying mechanism is still unclear. CD40L expression was measured in platelets from healthy subjects both with and without the addition of antioxidants or a phospholipase A2 (PLA2) inhibitor and in platelets from 2 patients with an inherited deficiency of gp91phox. Immunoprecipitation analysis was also performed to determine whether normal platelets showed gp91phox expression. Unlike catalase and mannitol, superoxide dismutase inhibited agonist-induced platelet CD40L expression in healthy subjects. Immunoprecipitation analysis also showed that platelets from healthy subjects expressed gp91phox. In 2 male patients with inherited gp91phox deficiency, collagen-, thrombin-, and arachidonic acid-stimulated platelets showed an almost complete absence of superoxide anion (O(2)(-)) and CD40L expression. Incubation of platelets from healthy subjects with a PLA2 inhibitor almost completely prevented agonist-induced O(2)(-) and CD40L expression. These data provide the first evidence that platelet CD40L expression occurs via arachidonic acid-mediated gp91phox activation.