Quantification of a novel dense granule protein (granulophysin) in
platelets of patients with dense granule storage pool deficiency
A Shalev, G Michaud, SJ Israels, A McNicol, S Singhroy, EM McMillan, JG White, CJ Witkop, WL Nichols and AH Greenberg
Department of Pediatrics, University of Manitoba, Winnipeg, Canada.
An antigen-capture sandwich enzyme-linked immunosorbent assay (ELISA) was
developed for a novel protein granulophysin, a constituent of the platelet
dense granule (DG) membrane and used to characterize patients with dense
granule storage pool deficiency (delta-SPD). The assay uses two monoclonal
antibodies against the protein, one of which is conjugated to peroxidase.
Purified DGs, an enriched source of the protein, were used for the standard
curve. Granulophysin levels were only low in forms of delta-SPD associated
with albinism. Granulophysin levels in platelet homogenates of 30 patients
with the Hermansky-Pudlak syndrome form of delta-SPD were 1/4 to 1/5 of
levels in controls or obligate heterozygotes. Two patients with the
Chediak-Higashi form of delta-SPD syndrome also had markedly reduced levels
of granulophysin. Patients with other forms of delta-SPD had normal levels
of granulophysin. Two sisters with delta-SPD in one family had normal
granulophysin present in empty dense granule membrane vesicles. Three
members of another family with delta-SPD had low DG counts but normal
granulophysin levels, indicating that in this group the level of
granulophysin was maintained despite the reduction in granule formation.
Thus, granulophysin quantitation facilitates characterization of delta-SPD
patients and may provide clues to the nature of defective granules in
delta-SPD subtypes.
Volume 80,
Issue 5,
pp. 1231-1237,
09/01/1992
Copyright © 1992 by The American Society of Hematology
