Platelet and neutrophil function and eicosanoid release in a subject with abetalipoproteinaemia

It has been suggested that plasma low density lipoprotein (LDL) may affect platelet and leukocyte activity and the release of biologically active eicosanoids which may contribute to the pathogenesis of coronary heart disease. To evaluate the possible biological effects of LDL further we have studied platelet aggregation, leukocyte function and eicosanoid release in a young woman with abetalipoproteinaemia (ABL) who totally lacks LDL. The subject showed decreased platelet response to threshold doses of ADP, collagen and arachidonic acid compared to a matched control measured in parallel or to a larger control group of 22 normal subjects. Aggregation was normal to higher doses of the same agonists. Thromboxane formation in clotted whole blood and in PRP stimulated with collagen was lower for the ABL subject than the control group. Neutrophil function assessed by chemiluminescence following stimulation with PMA, zymosan and FMLP was normal for the ABL subject, although the release of leukotriene B4 from calcium ionophore stimulated cells less than controls. Neutrophil platelet activating factor (PAF) formation and half life in plasma was not altered in ABL. The fatty acid composition of plasma, platelet and erythrocyte membrane phospholipids showed particularly low levels of linoleic acid in ABL compared to controls. Platelet phospholipids from the ABL subject also showed low levels of arachidonic acid. The decrease in eicosanoid formation seen in ABL may be the result of altered fatty acid composition of cell membrane phospholipids, or perhaps a defect in arachidonate mobilization. These results indicate that in a subject who lacks circulating LDL the behaviour of platelets and neutrophils in some in vitro tests is altered, although the extent to which these effects are reflected in vivo with regard to inflammatory and thrombotic mechanisms is not known.