Role of glycoprotein IIb-IIIa (alpha IIb beta 3-integrin) in stimulation of secretion from platelet granules

The involvement of glycoprotein (GP) IIb-IIIa (alphaIIbbeta3-integrin) in the stimulation of secretion from platelet dense and alpha-granules was investigated. Fibrinogen binding with GP IIb-IIIa and platelet aggregation were inhibited by fragments of anti-GP IIb-IIIa monoclonal antibodies (monAB)--...

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Veröffentlicht in:Biochemistry (Moscow) 2003-02, Vol.68 (2), p.209-216
Hauptverfasser: Naimushin, Ya A, Mazurov, A V
Format: Artikel
Sprache:eng
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Zusammenfassung:The involvement of glycoprotein (GP) IIb-IIIa (alphaIIbbeta3-integrin) in the stimulation of secretion from platelet dense and alpha-granules was investigated. Fibrinogen binding with GP IIb-IIIa and platelet aggregation were inhibited by fragments of anti-GP IIb-IIIa monoclonal antibodies (monAB)--Fab fragment of antibody c7E3 (preparation ReoPro) and F(abacute;)(2) fragment of antibody FraMon (preparation FRAMON). Suppression of GP IIb-IIIa receptor activity by both preparations led to 100% inhibition of [(14)C]serotonin secretion from dense granules upon platelet activation with ADP, to partial inhibition upon activation with thromboxane A(2) analog U46619 (by 60-70%) and thrombin at 0.1 U/ml (by 40-50%), but did not decrease serotonin secretion induced by thrombin at 1 U/ml. ReoPro and FRAMON completely inhibited ADP-induced release of soluble P-selectin from platelet alpha-granules, but did not influence P-selectin secretion stimulated by U46619 and by both thrombin concentrations. MonAB CRC54 against GP IIb-IIIa, which induced its interaction with fibrinogen and platelet aggregation, also stimulated serotonin and P-selectin secretion. Both types of release reactions were completely suppressed by ReoPro and FRAMON. Aspirin, the cyclooxygenase inhibitor, also prevented CRC54-induced secretion, proving the dependence of this process on thromboxane A(2) synthesis. Upon platelet activation by concanavalin A (Con A), caused by clusterization of membrane glycoproteins, GP IIb-IIIa blockade only slightly (by 15-20%) decreased serotonin secretion. High level of Con A-induced secretion was also detected in a patient with hereditary deficiency of GP IIb-IIIa. Thus, neither clusterization nor occupation of GP IIb-IIIa are essential for the stimulation of Con A-induced release reaction. The data indicate that GP IIb-IIIa binding with fibrinogen leads to the stimulation of secretion from platelet granules. When the level of secretion does not depend on GP IIb-IIIa interaction with the ligands or its presence on platelets full-scale release reaction is presumably stimulated by activating signals formed without GP IIb-IIIa involvement.
ISSN:0006-2979
1608-3040
DOI:10.1023/A:1022605613859