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Stimulation of P2 (P2X 7 ) receptors in human dendritic cells induces the release of tissue factor‐bearing microparticles
Author(s) -
Baroni Marcello,
Pizzirani Cinzia,
Pinotti Mirko,
Ferrari Davide,
Adinolfi Elena,
Calzavarini Sara,
Caruso Pierpaolo,
Bernardi Francesco,
Di Virgilio Francesco
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7238com
Subject(s) - tissue factor , receptor , microbiology and biotechnology , chemistry , microvesicles , coagulation , western blot , vesicle , stimulation , recombinant dna , biophysics , biochemistry , biology , membrane , medicine , endocrinology , microrna , gene
ABSTRACT Receptors for extracellular nucleotides are the focus of increasing attention for their ability to cause release of plasma membrane vesicles (micropar‐ticles, MPs). Here, we show that monocyte‐derived human dendritic cells (DCs) stimulated with a P2X 7 receptor (P2X 7 R) agonist undergo a large release of MPs endowed with procoagulant activity. Functional and Western blot studies revealed that MPs contain the membrane‐bound form of tissue factor (TF), a glycop‐rotein acting as essential cofactor of activated factor VII and triggering blood coagulation. Quiescent DCs express the membrane‐bound (full length), as well as truncated alternatively spliced TF forms. DC reactivity to anti‐TF Abs disappeared almost completely on stimulation with ATP or benzoyl ATP (BzATP), as shown by immunoblot and confocal microscopy analysis. Concurrently, TF reactivity and activity appeared in the vesicular fraction, indicating that MPs are important carriers for the dissemination of full‐length TF form. Activity of MP‐bound TF, comparable to that of relipidated recombinant TF, was dose dependently inhibited by the addition of a specific anti‐human TF antibody. We infer that a large fraction of this protein, and its procoagulant potential, are “deliverable” after physiological or pathological stimuli. These findings might have implications for triggering and propagating coagulation in healthy and atherosclerotic vessels.—MarcelloBaroni, CinziaPizzirani, MirkoPinotti, DavideFerrari, ElenaAdinolfi, SaraCalzavarini, PierpaoloCaruso, FrancescoBernardi, FrancescoDi Virgilio. Stimulation of P2 (P2X7) receptors in human dendritic cells induces the release of tissue factor‐bearing microparticles. FASEB J. 21, 1926–1933 (2007)