Regulation of platelet adhesion by oxidized lipoproteins and oxidized phospholipids.
Activated platelets adhere to the endothelium and release vasoactive mediators which induce vasoconstriction and remodeling of the vessel wall. The influence of native and ex vivo oxidized lipoproteins enriched with oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC), the major lipid responsible for the biological activity of minimally oxidized LDL (mm-LDL), on platelet adhesion, membrane receptor expression and aggregation was studied. Influence of native and oxidized lipoproteins (5-100 microg protein/ml); ox-PAPC (0.5-50 microg/ml); ADP (1-10 microM) as well as the specific phosphatase 1 and 2A inhibitor okadaic acid (3-10 microM) on platelet adhesion, receptor expression and aggregation was measured. Platelets adhered to all the classes of lipoproteins immobilized in plastic microtiter wells (native lipoproteins: HDL<LDL<VLDL<oxidized lipoproteins<ox-PAPC-enriched lipoproteins). Flow cytometry revealed that lipoproteins increased CD41 expression. Preincubation of platelets with ox-PAPC alone, significantly up-regulated CD62p and CD41 receptors (higher dose) but potently inhibited anti-CD36 MoAb binding. Okadaic acid increased anti-CD41 and decreased anti-CD36 and anti-CD42b MoAbs binding. Neither ox-PAPC nor okadaic acid induced platelet aggregation. CD36 seems to be the main receptor responsible for binding of oxidized lipoproteins, particularly its ox-PAPC epitope. The effect of okadaic acid on CD36 and CD41 argue for the participation of phosphorylation-dependent reorganization of cellular trafficking and microtubule organization by ox-PAPC.
Department of Clinical Biochemistry, Jagiellonian University Collegium Medicum Kraków, Poland.
Jadwiga
J
Hartwich
Aldona
A
Dembinska-Kieć
Anna
A
Gruca
Marcin
M
Motyka
Lukasz
L
Partyka
Joanna
J
Skrzeczyńska
Malgorzata
M
Bzowska
Juliusz
J
Pryjma
Joakim
J
Huber
Norbert
N
Leitinger
Gerd
G
Schmitz
D000244:Adenosine Diphosphate / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008074:Lipoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*
D015703:Antigens, CD; D008074:Lipoproteins; D010713:Phosphatidylcholines; D010743:Phospholipids; D000244:Adenosine Diphosphate