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(Circulation. 2004;110:1326-1329.)
© 2004 American Heart Association, Inc.

Original Articles

gp91phox-Dependent Expression of Platelet CD40 Ligand

P. Pignatelli, MD; V. Sanguigni, MD; L. Lenti, MD; D. Ferro, MD; A. Finocchi, MD; P. Rossi, MD; F. Violi, MD

From Divisione IV Clinica Medica (P.P., D.F., F.V.) and Dipartimento di Medicina Sperimentale e Patologia (P.P., L.L., F.V.), Università di Roma "La Sapienza," and Dipartimento di Medicina Interna (V.S.) and Dipartimento di Medicina Sperimentale (A.F., P.R.), Università di Roma Tor Vergata, Rome, Italy.

Correspondence to Francesco Violi, MD, Divisione IV Clinica Medica, Dipartimento di Medicina Sperimentale e Patologia, Università di Roma "La Sapienza," Policlinico Umberto I, 00185, Rome, Italy. E-mail Francesco.Violi{at}uniroma1.it

Received November 21, 2003; de novo received March 18, 2004; revision received May 20, 2004; accepted May 20, 2004.

Background— CD40 ligand (CD40L) expression on platelets is mediated by agonists, but the underlying mechanism is still unclear.

Methods and Results— 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 (O₂^–) and CD40L expression. Incubation of platelets from healthy subjects with a PLA2 inhibitor almost completely prevented agonist-induced O₂^– and CD40L expression.

Conclusions— These data provide the first evidence that platelet CD40L expression occurs via arachidonic acid–mediated gp91phox activation.

Key Words: CD40 ligand • NADPH oxidase • oxidative stress • platelets

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