Decreased content and surface expression of alpha-granule membrane protein GMP-140 in one of two types of platelet alpha delta storage pool deficiency.
To determine whether alpha-granule membranes are present in platelets of patients with storage pool deficiencies of both alpha and dense granules (alpha delta-SPD), we examined the content and surface expression of the alpha-granule membrane protein GMP-140 in one patient (J.C.) with a severe alpha-granule deficiency and in three members of a family (family C) with milder alpha-granule deficiencies. Surface expression of GMP-140 in stimulated platelets, assessed by flow cytometric measurements of the binding of two anti-GMP-140 monoclonal antibodies, was 24-38% of normal values in platelets from patient J.C., vs. 60-95% of normal values in family C. Total platelet content of GMP-140, determined in platelet lysates by antigen-capture ELISA, was 49% of normal in patient J.C., but normal in the members of family C. Platelets of patient J.C. were found to be heterogeneous with respect to GMP-140 content and surface expression by both flow cytometry and immunogold electron microscopy. Approximately 80% of her platelets expressed little or no GMP-140 after stimulation, whereas the remaining 20% expressed normal amounts of GMP-140 and showed extensive immunogold labeling of typical alpha-granules and clear vacuoles. No such heterogeneity was found in platelets from family C. These findings in the severe alpha delta-SPD patient are in clear contrast to the observations of normal GMP-140 content in the three other alpha delta-SPD patients, and in patients with the gray platelet syndrome, reported previously by others. These results illustrate the phenotypic heterogeneity of alpha-granule deficiencies in human platelets, and suggest that a defect in granule formation in the megakaryocytes may account for the alpha-granule defect in at least one form of alpha delta-SPD.
Lages
B
B
Department of Medicine, St. Luke's-Roosevelt Hospital Center, New York, NY 10019.
Shattil
S J
SJ
Bainton
D F
DF
Weiss
H J
HJ
D000328:Adult; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D008875:Middle Aged; D019007:P-Selectin; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D010981:Platelet Storage Pool Deficiency / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007074:Immunoglobulin G; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins