title: Specific binding of hypochlorite-oxidized HDL to platelet CD36 triggers proinflammatory and procoagulant effects.
abstract: OBJECTIVE
  Oxidative stress and systemic inflammation negatively affect several protective functions of high density lipoproteins (HDL) and oxidative modification of HDL by the inflammation-derived oxidant hypochlorite converts HDL into a potent platelet agonist. Therefore it was the aim of this work to clarify if these platelet-activating effects result from specific binding of hypochlorite-oxidized HDL (hyp-OxHDL) to the platelet surface and to identify responsible receptors.
  
  
  METHODS
  Binding and functional studies were performed with hyp-OxHDL in absence and presence of (potential) competitors in normal and CD36-deficient human platelets. Platelet aggregation was quantified by light transmission aggregometry. Surface expression of CD62P, phosphatidylserine and CD40L was quantified by flow cytometry.
  
  
  RESULTS
  Binding studies reveal that hyp-OxHDL show specific and saturable high-affinity binding to the platelet surface. Hyp-OxHDL trigger platelet aggregation and in a dose dependent way provoke the release of significant amounts of CD40L as well as phosphatidylserine on the platelet surface. Blocking specific binding of hyp-OxHDL to the platelet surface interferes with the ability of hyp-OxHDL to stimulate human platelets. CD36-deficient human platelets show markedly reduced binding of hyp-OxHDL. Upon addition of hypochlorite-oxidized HDL, CD36-deficient platelets do not aggregate and completely fail to release CD40L or phosphatidylserine.
  
  
  CONCLUSIONS
  From these results we conclude that specific binding of hyp-OxHDL to platelet CD36 is essential for the proinflammatory and procoagulant effects of hyp-OxHDL shown within this work. The contribution of other receptors besides CD36 to specific binding of hyp-OxHDL to the platelet membrane appears to be minimal, at best.
authors.affiliation: Institute of Physiology, Center for Physiology & Pharmacology, Medical University of Vienna, Schwarzspanierstr. 17, A-1090 Vienna, Austria.
authors.forename: Alice
authors.initials: A
authors.lastname: Assinger
authors.forename: Franz
authors.initials: F
authors.lastname: Koller
authors.forename: Werner
authors.initials: W
authors.lastname: Schmid
authors.forename: Maria
authors.initials: M
authors.lastname: Zellner
authors.forename: Rita
authors.initials: R
authors.lastname: Babeluk
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Koller
authors.forename: Ivo
authors.initials: I
authors.lastname: Volf
mesh_terms: D001667:Binding, Competitive; D001777:Blood Coagulation; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D018955:CD36 Antigens / Q000097:blood* / Q000172:deficiency; D023201:CD40 Ligand / Q000097:blood; D020013:Calcium Signaling; D005434:Flow Cytometry; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry*; D007249:Inflammation / Q000097:blood* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D019007:P-Selectin / Q000097:blood; D010718:Phosphatidylserines / Q000097:blood; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000097:blood; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D016877:Oxidants; D019007:P-Selectin; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D023201:CD40 Ligand; D006997:Hypochlorous Acid