Effect of endotoxin on arachidonic acid release and thromboxane B2 production by human platelets

Abstract

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 μg/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, the 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 < 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 < 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 < 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.