Inhibition of platelet-activating factor (PAF)-induced platelet aggregation by fatty acids from human saliva

Abstract

Experiments were undertaken to identify the nature of a previously identified inhibitor of PAF-induced platelet aggregation (PA) in human saliva. Human saliva fractionated by preparative thin layer chromatography (TLC) yielded a fraction that co-migrated with fatty acids (FAs) and inhibited PAF-induced aggregation of platelets. Synthetic FAs tested for their capacities to inhibit 0.1 nM PAF-induced PA showed that only the cis-unsaturated compounds were inhibitory with activities of some of the polyunsaturated FAs (PUFA) reaching almost 100% at 20 μM. Eicosapentanoic acid (EPA) and 8,11,14-eicosatrienoic acid also deaggregated the PAF-induced aggregates. With the exception of oleic acid (OLA), cis-monounsaturated FAs, and elaidic acid, the trans isomer of OLA, were poor inhibitors. In a direct comparison with other platelet agonists, ADP, thrombin, and ionophore A23187, the active saliva fraction and selected individual FAs inhibited, to greater or lesser extent, PA induced by each of the agonists. EPA, OLA, linoleic acid (LNA), and the active saliva fraction were potent inhibitors of ADP-induced PA, EPA completely inhibited thrombin-induced PA and the saliva fraction showed only weak – moderate inhibitory activity to both thrombin- and ionophore A23187-induced PA. Other reports of endogenous PAF inhibitors in mammalian tissues are compared to the present results. PAF can trigger and amplify inflammatory cascades suggesting a possible modulation role for cis-unsaturated FAs in some diseases.

Keywords:

• Fatty acids and platelets
• human saliva and PAF
• PAF inhibitors
• platelet-activating factor
• platelet aggregation inhibitors
• polyunsaturated fatty acids

Acknowledgements

We thank Sue Cooney for general discussions on the measurement of PAF.

Disclosure statement

The authors have no conflicts of interest to declare.

Author contributions

Conception of study: BAB, MAS

Design of study: BAB. MAS

Experimentation: MAS

Analysis of data: BAB, MAS

Figure and table preparation: MAS

Literature review: BAB, MAS

Preparation and final approval of manuscript: BAB, MAS

Additional information

Funding

This work was supported by the National Health and Medical Research Council of Australia.