alphaIIb beta 3-integrin mediated adhesion of human platelets to a fibrinogen matrix triggers phospholipase C activation and phosphatidylinositol 3',4'-biphosphate accumulation.
This study focused on the variations in phosphoinositide metabolism depending upon alphaIIbbeta3-integrin/fibrinogen interaction without previous activation of platelet agonist receptors. We found that adhesion of resting human platelets to immobilized fibrinogen stimulates phosphatidic acid production and a concomitant decrease in phosphatidylinositol 4',5'-bisphosphate. These results, and the absence of a transphosphatidylation reaction, argue in favor of the activation of a phospholipase C. Moreover, we observed the accumulation of phosphatidylinositol 3',4'-bisphosphate in adherent platelets as a consequence of the activation of a phosphatidylinositol 3-kinase. This effect was inhibited by ADP scavengers. Our results demonstrate that in adherent platelets, whereas phosphatidylinositol 3-kinase activation is controlled by both alphaIIbbeta-integrin engagement and released ADP, phospholipase C stimulation is triggered only by alphaIIbbeta-integrin/fibrinogen interaction.
Gironcel
D
D
INSERM U 326, Hôpital Purpan, Toulouse, France.
Racaud-Sultan
C
C
Payrastre
B
B
Haricot
M
M
Borchert
G
G
Kieffer
N
N
Breton
M
M
Chap
H
H
D000244:Adenosine Diphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C060980:phosphatidylinositol 3,4-diphosphate; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D010738:Type C Phospholipases