13-hydroxy-9-11-octadecadienoic-acid and 12-hydroxy-5-8-10-heptadecatrienoic-acid

We have recently demonstrated a novel cytotoxic effect of human platelets against Toxoplasma gondii and a role for thromboxane (TX) in this process (Yong et al., 1991). We now report on the spectrum of lipid mediators released by human platelets after interaction with T. gondii. In addition to TXB2, human platelets after incubation with T. gondii for 90 min released 12-hydroxyheptadecatrienoic acid (12-HHT), 12-hydroxyeicosatetraenoic acid (12-HETE), and an unidentified peak (UVmax 234 nm) as determined by reverse-phase high-performance liquid chromatography. Thermospray-liquid chromatography/mass spectrometry analysis and straight-phase HPLC identified the unknown peak as a mixture of 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE. Radiolabeling studies with [14C]linoleic acid indicated that the platelets were the cellular source of the octadecanoids with 13-HODE (87.7%) greater than 9-HODE (12.3%). Inhibitor studies with indomethacin indicated that 13-HODE was a lipoxygenase product and 9-HODE was a cyclooxygenase product of linoleic acid. Thus, Toxoplasma-stimulated platelets release oxygenated products of both arachidonic acid and linoleic acid which may be important in the host response to T. gondii infection.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Blood Platelets; Chromatography, High Pressure Liquid; Fatty Acids, Unsaturated; Gas Chromatography-Mass Spectrometry; Hydroxyeicosatetraenoic Acids; Indomethacin; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Platelet Activation; Stereoisomerism; Toxoplasma

Non-stimulated guinea-pig pulmonary macrophages (PM) convert arachidonic acid to thromboxane B2 and 12-hydroxy-heptadecatrienoic acid, whereas linoleic acid is metabolized to two hydroxy compounds, i.e. 9-hydroxy- and 13-hydroxy-octadecadienoic acid. Coincubation of PM with immune serum (2% v/v) resulted in a profound reduction of the release of these products. This effect seemed to be due to an inhibitory action on cyclooxygenase activity. Control serum also possessed inhibitory properties towards the release of fatty acid metabolites, possibly due to an effect on phospholipase activity. Because of the radical scavenging properties of 9-hydroxy-octadecadienoic acid, the modulation of the release of this product may be an important determinant in macrophage function.

Topics: Animals; Fatty Acids; Fatty Acids, Unsaturated; Guinea Pigs; Immune Sera; Linoleic Acids; Linoleic Acids, Conjugated; Lung; Macrophages; Male