AMINOPHOSPHOLIPID EXPOSURE, MICROVESICULATION AND ABNORMAL PROTEIN-TYROSINE PHOSPHORYLATION IN THE PLATELETS OF A PATIENT WITH SCOTT-SYNDROME - A STUDY USING PHYSIOLOGICAL AGONISTS AND LOCAL-ANESTHETICS

The Scott syndrome is a rare inherited haemorrhagic disorder character ized by the inability of blood cells to expose aminophospholipids and to shed microparticles. We have had the opportunity to study a recentl y reported French patient with this syndrome and have confirmed by mea ns of a fluorescence assay for transbilayer lipid movement a reduced a minophospholipid exposure when platelets were stimulated with the calc ium-ionophore ionomycin, in spite of a normal elevation of intracellul ar Ca2(+). Secretion and calpain activation were also shown to be norm al. Significantly, the level of phosphotyrosine-labelled proteins in p latelets treated with thrombin or a thrombin + collagen mixture and in particular the phosphorylation of a 40 kD band were severely reduced. Furthermore, inhibition of thiol-containing enzymes, including tyrosi ne-phosphatases, by N-ethyl maleimide did not lead to aminophospholipi d exposure in the patient's platelets, in spite of increased tyrosine protein phosphorylation. In contrast, amphiphilic membrane drugs such as tetracaine and propranolol induced both surface aminophospholipid e xposure in Scott platelets and the shedding of microparticles, thereby showing that membrane perturbation can lead to loss of phospholipid a symmetry in this syndrome. Our results provide the first insight that the lack of expression of procoagulant phospholipids and microparticle formation in Scott syndrome platelets is associated with a defect of intracellular signalling.