Arachidonate transfer between platelets and lipoproteins.
Although platelets have specific bindingsites for LDL and HDL, it is doubtful whether lipoproteins modulate platelet functions via receptor-mediated processes. We investigated platelet-lipoprotein interaction during prolonged incubation with concentrations of LDL and HDL that saturate the bindingsites within a few minutes. When [3H]arachidonate-labeled human platelets were incubated for 4 h with lipoproteins, part of the 3H-radioactivity transferred to LDL and to a lesser extent to HDL. The transfer was temperature-sensitive, unaffected by modification of lysine in LDL or indomethacin treatment of the platelets, and almost irreversible. [3H]arachidonate transfer to lipoproteins could be mimicked by incubating platelets with a high concentration of fatty acid free albumin. This showed, that the loss of 3H-radioactivity reflected a decrease in endogenous arachidonate, leading to impaired aggregation, secretion and thromboxane B2 formation in platelets after stimulation with thrombin but not with arachidonate. Thus, the decrease in platelet functions seen after long incubation with HDL is caused by depletion of platelet arachidonate. Despite an even stronger arachidonate depletion by LDL, this lipoprotein initiated arachidonate metabolism and secretion independent of specific binding sites for LDL on the platelet. Surprisingly, the major part of the secretion was preserved when the formation of prostaglandin endoperoxides/thromboxane A2 was inhibited with indomethacin. These findings argue against a role for LDL and HDL receptors in the modulation of platelet functions and are more in favor of lipid exchange processes between platelets and lipoproteins.
Surya
I I
II
Department of Haematology, University Hospital Utrecht, The Netherlands.
Gorter
G
G
Akkerman
J W
JW
D000255:Adenosine Triphosphate / Q000378:metabolism; D016718:Arachidonic Acid / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012709:Serum Albumin; D016718:Arachidonic Acid; D012701:Serotonin; D013929:Thromboxane B2; D000255:Adenosine Triphosphate