Efficient platelet delta-granule release induced by [Ca2+]i elevation is modulated by GPIIbIIIa.
Intracellular Ca2+ elevation generates a cascade of events that leads to platelet activation and degranulation. The GPIIbIIIa-ligand molecular complex plays a central role in several aspects of platelet activation. Taking advantage of the flow cytometric simultaneous analysis of surface GPIIbIIIa expression and intracellular serotonin content, we demonstrate here that the functional inhibition of GPIIbIIIa generates an impairment of delta-granule release even upon maximal intracellular Ca2+ elevation. In healthy subjects, the GPIIbIIIa inhibitor tirofiban impairs platelet delta-granule release. Analogously, Glanzmann thrombasthenia patients show an impairment of delta-granule release that is proportional to their residual expression of platelet GPIIbIIIa. These data show that platelet surface expression of functional GPIIbIIIa is required for a fully efficient secretion of delta-granules and serotonin release. The implications of our findings are discussed in the light of the complex interplay between vesicle release and ligand-receptor triggering during platelet activation.
Gobbi
Giuliana
G
Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Parma, Italy.
Sponzilli
Ivonne
I
Mirandola
Prisco
P
Tazzari
Pier Luigi
PL
Caimi
Luigi
L
Cacchioli
Antonio
A
Matteucci
Alessandro
A
Giuliani Piccari
Gabriella
G
Cocco
Lucio
L
Vitale
Marco
M
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D013915:Thrombasthenia / Q000097:blood
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D002118:Calcium