Hypochlorite-oxidized LDL induces intraplatelet ROS formation and surface exposure of CD40L-A prominent role of CD36

Objective: OxLDL represents a central player in atherogenesis and has been shown to activate human blood platelets. In light of the pivotal role of CD40L in inflammation, it was the aim of this work to clarify if platelet-activating effects of oxidized LDL result in surface exposure and liberation of CD40L and to explore the role of platelet scavenger receptor CD36 in this process. Methods: Binding and functional studies were performed with hypochlorite-oxidized LDL in absence and presence of (potential) competitors in normal and CD36-deficient human platelets. To determine functional effects of hypochlorite-oxidized LDL on human platelets, formation of reactive oxygen species, intraplatelet calcium, CD40L and CD62P as well as platelet aggregation were quantified. Results: Addition of OxLDL to resting human platelets results in intracellular calcium flux, platelet aggregation and surface expression of CD62P. OxLDL triggers the formation of intracellular reactive oxygen species and surface exposure of CD40L, with both being sensitive to the NADPH oxidase inhibitor apocynin. In CD36-deficient human platelets, functional effects as well as high affinity binding of hypochlorite-oxidized LDL appears to be significantly reduced compared with platelets positive for CD36. Conclusions: Our results prove a prominent - however, not exclusive - role of CD36 in platelet binding of hypochlorite-oxidized LDL. CD36 appears to be the major receptor responsible for hypochlorite-oxidized LDL-induced platelet activation that accumulates in the release of CD40L. As platelets represent the major source of CD40L, our findings emphasize an important pro-inflammatory role of platelets, especially in conditions of oxidative stress. (C) 2010 Elsevier Ireland Ltd. All rights reserved.