Inhibition of platelet function by cis-unsaturated fatty acids
DE MacIntyre, RL Hoover, M Smith, M Steer, C Lynch, MJ Karnovsky and EW Salzman
The uptake of free fatty acids has previously been shown to affect the
capping of lymphocytes, and there is evidence that different types of fatty
acids may partition into separate lipid domains in cell surface membranes.
In studies of gel-filtered human platelets, we found that cis-unsaturated
fatty acids (1-35 microM) inhibited platelet shape change, aggregation, and
secretion of 5-hydroxytryptamine induced by thrombin, adenosine diphosphate
(ADP), collagen, U46619 (a thromboxane A2 analog), or plant lectins, but
not that induced by A23187, a calcium ionophore. Trans-unsaturated and
saturated fatty acids had little or no inhibitory effect. The inhibitory
effects of cis-unsaturated fatty acids were not affected by inhibition of
adenylate cyclase or cyclooxygenase. 14C-labeled fatty acids were taken up
into platelet lipids. The maximum platelet-inhibitory effect of
cis-unsaturated fatty acids was seen when over 90% of the platelet label
was still in the form of free fatty acids. Platelet inhibition could be
reversed by washing the platelets by gel filtration. Binding of platelet
agonists to the platelet was not inhibited by the fatty acids.
Cis-unsaturated fatty acids, but not trans-unsaturated or saturated fatty
acids, decreased fluorescence polarization of platelets or isolated
platelet membranes monitored with 1,6-diphenyl- 1,3,5-hexatriene. The
potency of the fatty acids as inhibitors of platelet aggregation was
inversely correlated with their melting points. These data suggest that
inhibition of receptor-mediated platelet responses by cis-unsaturated fatty
acids results from perturbation of the platelet membrane in specific lipid
domains.
Volume 63,
Issue 4,
pp. 848-857,
04/01/1984
Copyright © 1984 by The American Society of Hematology
