Effect of endotoxin on arachidonic acid release and thromboxane B2 production by human platelets.
Plasma thromboxane A2, which is elevated during endotoxemia, has previously been shown to be a major factor contributing to the mortality and morbidity that occurs in endotoxin shock in the experimental animal. Using a minimal dose of Escherichia coli endotoxin (1 microgram/ml), we have demonstrated that the preincubation of human platelets with endotoxin induces changes in platelet arachidonic acid release and the subsequent conversion of the released arachidonic acid to thromboxane B2, and stable end product of thromboxane A2. In paired experiments, in the presence of endotoxin, the addition of the aggregating agent thrombin (0.5 U/ml) caused human platelets to release 29.1 +/- 3.4% of 14C-arachidonic acid from prelabeled platelet phospholipids. This value was significantly elevated (p less than 0.02) when compared with the release of 14C-arachidonic acid from platelets in the absence  of endotoxin (21.9 +/- 3.6%). Similarly, comparison of the results of the conversion of the released arachidonic acid to platelet thromboxane B2 (TxB2) revealed that TxB2 production was significantly increased (P less than 0.01) when human platelets were preincubated with endotoxin prior to the addition of thrombin (6.1 +/- 0.6%) when compared with TxB2 formation observed in the absence of endotoxin (3.4 +/- 0.5%). The absolute amount of released arachidonic acid that was converted to TxB2 in the presence of endotoxin (1.8 +/- 0.3%) was also significantly higher (P less than 0.01) than the value observed in its absence (0.8 +/- 0.2%) was also significantly higher (P less than 0.01) than the value observed in its absence (0.8 +/- 0.2%). This study suggests that one of the tissue sources of the proaggregatory vasoconstrictor thromboxane A2 during endotoxemia is the platelet.
D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D004731:Endotoxins; D013931:Thromboxanes; D013929:Thromboxane B2; D013917:Thrombin