Membrane Glycoprotein Defects In Bernard-Soulier Syndrome Platelets

Abstract

It is well established that Bernard-Soulier syndrome (BSS) platelets are deficient in a major membrane glycoprotein (lb). In order to investigate if this is the only defect in this disorder and to see if the β-subunit of glycoprotein lb is also diminished, platelets from 3 BSS patients and from healthy donors were isolated, washed and surface labelled by lactoperoxidase-catalysed iodination, pèriodate/NaB3H4 or neuraminidase/ galactose oxidase/NaB3H4. Labelled platelets were solubilized in sodium dodecyl sulphate and separated by 2-dimensional gel electrophoresis (isoelectric focusing, discontinuous polyacrylamide gel electrophoresis). Glycoprotein Ibα was virtually absent in 2 patients and strongly decreased in the third patient. The 3-subunit was also absent in the 2 patients and present at about 40 % of normal in the third. Glycoprotein IIbβ was present normally in all patients. In addition, a further low molecular weight glycoprotein with a M.WT. of 17,000 and a pI of 6.8-7.5 was absent or present at levels paralleling glycoprotein Ibβ. The thrombin cleavable glycoprotein (GP IV or V) appeared greatly diminished with BSS platelets labelled by carbo-hydrate specific methods though no difference could be seen with iodination. This finding was confirmed in a fourth BSS patient using one dimensional gel electrophoresis.The defects in BSS platelets are thus more complex than previously thought.