Involvement of the Glycoproteic Ib-V-IX Complex in Nickel-Induced Platelet Activation

We studied the effect of nickel ions on platelet function because hypernickelemia has been found in patients with acute myocardial infarction. We previously demonstrated that nickel can activate an intracellular pathway leading to cytoskeleton reorganization consequent to tyrosine phosphorylation of...

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Bibliographic Details
Published in:Environmental health perspectives 2001-03, Vol.109 (3), p.225-228
Main Authors: Riondino, Silvia, Pulcinelli, Fabio Maria, Pignatelli, Pasquale, Gazzaniga, Pier Paolo
Format: Article
Language:English
Subjects:
Aggregation
Agonists
Cytoskeleton
Cytoskeleton - drug effects
Cytoskeleton - physiology
Environmental health
Environmental Pollutants - pharmacology
Humans
Immunoblotting
Integrins
Myocardial Infarction - etiology
Nickel - pharmacology
Occupational Exposure - adverse effects
Phosphatidylinositols
Platelet activation
Platelet Activation - drug effects
Platelet aggregation
Platelet Glycoprotein GPIb-IX Complex - drug effects
Platelet Membrane Glycoproteins
Platelets
Receptors
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Summary:We studied the effect of nickel ions on platelet function because hypernickelemia has been found in patients with acute myocardial infarction. We previously demonstrated that nickel can activate an intracellular pathway leading to cytoskeleton reorganization consequent to tyrosine phosphorylation of p60 src in human platelets independently of integrin alpha- IIb-beta3 (αIIbβ3). Moreover, in von Willebrand factor-stimulated platelets, the tyrosine phosphorylation of pp60 csrc is closely associated with the activation of phosphatidylinositol 3-kinase (PIK), and two adhesion receptors, glycoprotein (Gp)Ib and GpIIb/IIIa (αIIbβ3), are involved. In our study, 1 and 5 mM nickel in the presence of fibrinogen induced platelet aggregation (independently of protein kinase C activation) and secretion. The pretreatment with a PIK inhibitor, wortmannin, strongly decreased nickel-induced platelet aggregation. Platelet treatment with mocarhagin, a cobra venom metalloproteinase that cleaves GpIba, significantly reduced aggregation induced by 5 mM without affecting the response to other agonists such as adenosine diphosphate (ADP). Moreover, nickel caused PIK translocation to the cytoskeleton. Taken together, these observations suggest a partial involvement of both integrins αIIbβ3 and GpIb-V-IX complex in Ni2+-induced platelet activation.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.01109225