Iron-Dependent Human Platelet Activation and Hydroxyl Radical Formation Involvement of Protein Kinase C

Background—Iron is an important modulator of lipid peroxidation, and its levels have been associated with the progression of atherosclerosis. Little is known about the possibility that this metal, when released from tissue stores, may modulate the reactivity of blood cell components, in particular platelets. Therefore, we investigated a possible link between iron, oxygen free radical formation, and platelet function. Methods and Results—Human whole blood was stimulated with collagen 2 μg/mL, and an irreversible aggregation with thromboxane (Tx)B2 formation was observed (15±4 versus 130±10 ng/mL). Deferoxamine (DSF), a specific iron chelator, and catalase, an H2O2 scavenger, inhibited collagen-induced whole-blood aggregation. The aggregation was accompanied by an increase in hydroxyl radical (OH·) levels (30±8 versus 205±20 nmol/L dihydroxybenzoates), which were reduced by DSF and by 2 specific OH· scavengers, mannitol and deoxyribose. Iron (Fe2+) dose-dependently induced platelet aggregation, TxB2 formati...