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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1907.)
© 2006 American Heart Association, Inc.

Thrombosis

Human Platelets Secrete the Plasma Type of Platelet-Activating Factor Acetylhydrolase Primarily Associated With Microparticles

John V. Mitsios; Maria P. Vini; Dominique Stengel; Ewa Ninio; Alexandros D. Tselepis

From the Laboratory of Biochemistry, Department of Chemistry (J.V.M., M.P.V., A.D.T.), University of Ioannina, Greece; and INSERM U525 (D.S., E.N.), Université Pierre et Marie Curie-Paris 6 and Faculté de Médecine Pierre et Marie Curie, Paris, France.

Correspondence to Dr Alexandros D. Tselepis, MD, PhD, Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece, 45110. E-mail atselep{at}uoi.gr

Objective— Platelet-activating factor acetylhydrolase (PAF-AH) expresses a Ca²⁺-independent phospholipase A₂ activity and hydrolyzes platelet-activating factor as well as oxidized phospholipids. Two major types of PAF-AH have been described: the plasma type, which is associated with lipoproteins, and the intracellular type II PAF-AH.

Methods and Results— We investigated the type(s) of PAF-AH expressed in human platelets as well as the mechanism and the enzyme type secreted from platelets during activation. The majority of the enzyme activity (75.1±14.3% of total) is found in the cytosol, whereas 24.9±7.3% is associated with the membranes. Immunofluorescence microscopy studies and Western blotting analysis showed that platelets contain the plasma type as well as the intracellular type II PAF-AH. Furthermore, platelets contain high levels of the mRNA of plasma PAF-AH, whereas only a small quantity of the type II PAF-AH mRNA was detected. On activation, platelets secrete the plasma type of PAF-AH mainly associated with platelet-derived microparticles (PMPs). The enzyme activity was also detected on circulating PMPs in plasma from normolipidemic healthy subjects.

Conclusion— This is the first indication that in addition to lipoproteins, PAF-AH in human plasma is carried by PMPs, suggesting that the PMP-associated PAF-AH may play a role in the dissemination of biological activities mediated by these particles.

Activated platelets secrete the plasma type of platelet-activating factor acetylhydrolase (PAF-AH) primarily associated with platelet-derived microparticles (PMPs) in vitro. Importantly, the enzyme activity is also detected on circulating PMPs in normolipidemic plasma, suggesting that the PMP-associated PAF-AH may play a role in the dissemination of biological activities mediated by these particles.

Key Words: atherosclerosis • inflammation • PAF • PAF-acetyhydrolase • PMPs

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