title: Nickel enhances collagen-induced platelet activation acting by increasing the organization of the cytoskeleton.
abstract: In keratinocytes, osteoclasts and enterocytes, Ni2+ acts as an agonist working through selective activation of the polyvalent cation-sensing receptor. We report here that while Ni2+ alone had no direct ability to induce platelet aggregation or secretion, Ni2+ pretreatment produced these responses when platelets were stimulated with subthreshold concentrations of collagen. In addition, pretreatment with Ni2+ significantly enhanced collagen-induced phospholipase C activation and calcium mobilization. Platelet adhesion to collagen was increased and the inhibition of collagen-induced adhesion normally seen after cytochalasin D treatment was significantly diminished. When Ni2+ was added to platelets alone, tyrosine phosphorylation of p60src was increased. Moreover, Ni2+ enhanced the amount of protein, especially actin, found in the low-speed Triton X-100 insoluble cytoskeleton. Our results indicate that nickel, possibly acting via a platelet cation sensing receptor analogous to that which has been described in other cell types, may cause a rapid tyrosine kinase-dependent cytoskeleton reorganization leading to enhanced adhesion of platelets to collagen and increasing collagen-dependent responses.
authors.affiliation: Dept. of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
authors.forename: F M
authors.initials: FM
authors.lastname: Pulcinelli
authors.forename: S
authors.initials: S
authors.lastname: Sebastiani
authors.forename: M
authors.initials: M
authors.lastname: Pesciotti
authors.forename: P
authors.initials: P
authors.lastname: Pignatelli
authors.forename: P P
authors.initials: PP
authors.lastname: Gazzaniga
authors.forename: J L
authors.initials: JL
authors.lastname: Daniel
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004357:Drug Synergism; D006801:Humans; D009532:Nickel / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects
chemical_list: D009532:Nickel; D003094:Collagen